Chiral Oxaziridines Research Articles

Diastereoselective synthesis, binding affinity for vitamin D receptor, and chiral stationary phase chromatography of hydroxy analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol.

A series of analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol were obtained with an additional hydroxyl in the aliphatic side chain at carbon atom C-24. These analogs were synthesized by direct and diastereo-selective alpha-hydroxylation of enolates derived from respective vitamin D esters using Davies chiral oxaziridines. The use of (+)-(2R,8aS)-(8, 8-dichlorocamphoryl)sulfonyl oxaziridine resulted in (R) stereochemistry of the new asymmetric center for both series of analogs. Similarly, (-)-(2S,8aR) oxaziridine gave (S) analogs. The diastereomeric purity of hydroxy analogs was determined by high-performance liquid chromatography on a chiral stationary phase. High diastereopurity of hydroxylation of vitamin D esters was obtained without the use of any chiral auxiliary. The binding affinity of (24R)-1,24,25-trihydroxycholecalciferol for the calf thymus intracellular vitamin D receptor was one order of magnitude higher than that of the respective (24S)-diastereomer.

Diastereoselective synthesis, binding affinity for vitamin D receptor, and chiral stationary phase chromatography of hydroxy analogs of 1,25‐dihydroxycholecalciferol and 25‐hydroxycholecalciferol

A series of analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol were obtained with an additional hydroxyl in the aliphatic side chain at carbon atom C-24. These analogs were synthesized by direct and diastereo-selective α-hydroxylation of enolates derived from respective vitamin D esters using Davies chiral oxaziridines. The use of (+)-(2R,8aS)-(8,8-dichlorocamphoryl)sulfonyl oxaziridine resulted in (R) stereochemistry of the new asymmetric center for both series of analogs. Similarly, (−)-(2S,8aR) oxaziridine gave (S) analogs. The diastereomeric purity of hydroxy analogs was determined by high-performance liquid chromatography on a chiral stationary phase. High diastereopurity of hydroxylation of vitamin D esters was obtained without the use of any chiral auxiliary. The binding affinity of (24R)-1,24,25-trihydroxycholecalciferol for the calf thymus intracellular vitamin D receptor was one order of magnitude higher than that of the respective (24S)-diastereomer. Chirality 11:701–706, 1999. © 1999 Wiley-Liss, Inc.

ChemInform Abstract: Synthesis of cis‐δ‐Phenylmethyl‐D‐proline Using a Nitrogen‐ Centered Radical Derived from a Chiral Oxaziridine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of cis-δ-phenylmethyl- d-proline using a nitrogen-centered radical derived from a chiral oxaziridine

Oxaziridines react with Cu(I) salts to afford products resulting from the initial formation of a nitrogen-centered radical/oxygen-centered anion pair. For an α-aryl radical, a chiral pyrrolidine was obtained with high enantioselectivity and was transformed into cis-δ-phenylmethyl- d-proline. 3-Carbomethoxy-or 3-(2′-furyl)-substitution gave products resulting from β-cleavage or C→N migration, respectively.

Multinuclear magnetic resonance study of oxaziridines

AbstractNMR data (13C, 15N, 17O) for the three ring atoms of various oxaziridines are compared. Their significance for the prediction of the enantioselectivity of the oxidation of sulphides by chiral oxaziridines is discussed.

Microbiological and chemical methods in the asymmetric oxidation of sulfides: A comparative study for the preparation of ( S)-vinyl sulfoxides

The enantiogenicity of biological and chemical oxidation at the sulfur atom was studied on a series of prochiral vinyl sulfides for the preparation of sulfoxides of ( S)-absolute configuration. Using either fungal cultures, Sharpless-modified reagent or chiral oxaziridine, the enantiomeric excesses varied according to the substrate's steric and/or electronic structure; the three methods were complementary.

Asymmetrische Synthese chiraler Phosphorverbindungen durch destruktiv‐Oxidation von P(III)‐Verbindungen mittels chiraler Oxaziridine

Asymmetric Synthesis of Chiral Phosphorus Compounds by Destructive-Selective Oxidation of P(III) Compounds by Means of Chiral Oxaziridines From camphor and fenchone chiral N -sulfonyloxaziridines (e.g, 7,13) are available that are well-suited for the destructive-stereoselective oxidation of P(III) compounds 16. Optimum reagents and reaction conditions for this oxidation are determined by a systematic study. Chiral P(III) and P(V) compounds can thus be prepared from racemic P(III) derivatives.

Chiral liquid‐crystalline side chain polymers by enantioselective modification of prochiral parent polymers

AbstractThe preparation is reported of two side chain polyacrylate samples 1a,b containing a sulfide group linked to the mesogenic core. By oxidation with a preferentially chiral oxaziridine, samples 1a,b were chemoselectively and enantioselectively converted to the corresponding sulfoxide containing polymers 2a,b with an estimated 20% asymmetric induction. The mesophasic behaviour of the parent and oxidized polymer samples is analyzed by thermal and optical techniques. The modification of the prochiral sulfide groups into chiral sulfoxide groups slightly depresses the propensity of the resulting polymers to give stable and persistent mesophases.

The mechanism of oxygen transfer from an oxaziridine to a sulfide and a sulfoxide: a theoretical study

Chiral oxaziridines provide synthetically useful reagents for the asymmetric transfer of an oxygen atom to a variety of substrates. One of the fundamental questions pertaining to the approach of the reactants is whether either of the lone pairs on the electrophilic oxygen exerts a significant electronic influence on the transition structure. Employing a model reaction system, we have found that oxygen atom transfer from an oxaziridine to a sulfoxide is essentially invarient to the torsional orientation of the two fragments in the transition state. The planar and spiro transition structures differ in energy by only 0.4 kcal/mol at the MP4SDTQ/4-31G(d) level of calculation

ChemInform Abstract: Synthesis and Structure of a New Chiral Oxaziridine from (3‐Oxo‐camphorsulfonyl)imine.

AbstractOxidation of the camphor derivative (I) by magnesium monoperoxyphthalate affords the novel title compound (II) with an oxygen atom inserted in the cyclohexane moiety of (I).

Preparation and conformational studies of chiral camphor-derived oxaziridines

The syntheses and properties of new chiral N-sulphonyloxaziridines based on (–)-(camphorsulphonyl)-imine modified in position 3 of the camphor skeleton are reported. The preferred conformations of the 3-spiro-acetals and -thioacetals have been studied by NOE measurements.

Synthesis and Structure of a New Chiral Oxaziridine from (3-Oxo-camphorsulfonyl)imine

Oxidation of (3-oxo-camphorsulfonyl)imine (1) by magnesium monoperoxyphthalate does not lead to the oxaziridine obtained with 3-chloro-perbenzoic acid, but to a new chiral oxaziridine containing an additional oxygen atom (Baeyer-Villiger type oxidation). The structure of the product is established by X-ray crystallography, and reaction pathways for the oxidation of 1 by peracids are discussed.

Phosphite Oxidation and the Preparation of Five-Membered Cyclic Phosphorylating Reagents Via the Phosphites

Abstract The oxaziridines oxidize smoothly phosphites and other P(III) compounds; with chiral oxaziridines the oxidation is enantioselective. Some cyclic phosphorylating reagents are synthetized via the phosphites. The five-membered cyclic phosphorylating reagents 1 show some promise for the development of automated solid phase syntheses of DNA segments by direct phosphorylation. With 0,N,S as P-connected ring atoms and at least one sp2- carbon as a ring member, the computer program IGOR1,2 generated 278 constitutional formulas 1. Since certain thiol phosphates have favorable cleavage properties3, la and lb are particularly interesting candidates to be synthetized4 and to be tested as five-membered cyclic phosphorylating reagents for oligonucleotide syntheses.

ChemInform Abstract: Selectivity in an Asymmetric Nitrogen Insertion Process.

AbstractThe prochiral cyclohexanones (I) are converted to the axially chiral oxaziridines (IV) which are obtained as a mixture of four possible stereoisomers.

ChemInform Abstract: Asymmetric Oxidation of Chiral Enolates in the Preparation of Acyclic Tertiary α‐Hydroxy Amides in High Optical Purity.

AbstractThe lithium enolates of the carboxylic acid derivatives (I) are oxidized with the chiral oxaziridine (II) to give the optically active α‐hydroxy carboxylates or carboxamides (III).

X-Ray absolute configuration and circular dichroic properties of a chiral oxaziridine containing two phenyl chromophores in a trans configuration. Application of the circular dichroism exciton chirality method to the optical activity of (S,S)–(-)-3-phenyl-2-phenylsulphonyloxaziridine

Bijvoet X-ray diffraction analysis of crystalline, optically pure 3-phenyl-2-phenylsulphonyloxaziridine (–)-(2), obtained by asymmetric oxidation of the corresponding prochiral N-benzylidenephenyl-sulphonylimine (1) with (1S)-(+)-peroxycamphoric acid, followed by fractional crystallization of the crude reaction product, shows that the absolute configuration at the chiral nitrogen and carbon atoms of the oxaziridine ring is (2S,3S). Absolute configuration of (2) was also determined independently by application of the circular dichroism exciton chirality method.

Unusual spectroscopic and conformational properties of some spirocyclic oxaziridines

The proton that bears a 1,3-diaxial relationship to the substituted nitrogen atom of some chiral oxaziridines appears in the NMR spectrum at unusually high field. This observation indicates that an unusual rotamer is substantially populated in these systems.

Optical resolution of chiral N-alkyl-3,3-bismethoxycarbonyloxaziridines

Classical optical resolution by fractional crystallization of diastereoisomeric salts obtained from the reaction of racemic N-t-butyl-(3a) and N-isopropyl-oxaziridine-3,3-dicarboxylic acid monomethyl ester (3b) with (R)-(+)- and (S)-(–)-1-phenylethylamine, followed by methylation of the optically active (3a) and (3b), affords chiral oxaziridines (2a) and (2b) whose asymmetry is due solely to the nitrogen atom.

Dynamic stereochemistry of imines and derivatives. Part 18. Photosynthesis and photoracemization of optically active oxaziridines

Optically active oxaziridines have been synthesized with a maximum optical yield of 31% by photoisomerization (λ > 300 nm) of achiral aldo- and keto-nitrones in the presence of the chiral solvent (+)-(S) or (–)-(R)-2,2,2-trifluoro-1-phenylethanol. Photorearrangement of chiral nitrones to optically active oxaziridines was found to occur in achiral solvents with an optimum diastereoisomeric excess of 20%. Temperature, solvent and substituent effects upon the degree of asymmetric synthesis of chiral oxaziridines from the corresponding nitrone isomers have been examined.

Asymmetric synthesis at nitrogen by oxidation of imines with m-chloroperbenioic acid in the presence of optically active carbinols. Absolute stereochemistry of chiral alcohol-imine-peracid solvates

Optically active oxaziridines, stable at the asymmetric nitrogen atom, have been obtained by oxidation of imines with m-chloroperbenzoic acid in the presence of chiral carbinols. The optical purity of the reaction products increases on decreasing the temperature and depends on the starting imine and on the nature and relative amount of the chiral solvent. The absolute stereochemistry of the oxaziridines obtained is correlated with the chirality of the alcohol used. Specific carbinol–imine solvation models are discussed in the light of enantiomeric 1H n.m.r. nonequivalence and asymmetric reaction results, obtained by using chiral trifluoromethylcarbinols, imine substrates, and oxaziridine products of well established configuration.