Oxaziridine stereochemistry

An active-site model has been proposed to explain the high asymmetric oxidation of sulfide to sulfoxides75 (Fig. 6). The model consists of three pockets, A, B, and C, where pocket B, defined by the two chlorine atoms and the phenylsulfonyl group, is responsible for the high enantioselectivity exhibited for the oxidation of sulfides Rl-S-Rs. The absolute stereochemistry of the final sulfoxides is predicted in terms of a simple steric model, which involves minimization of nonbonded interaction between the RL and Rs groups of the sulfides (RL-S-Rs) and the active site surface of the oxaziridine in an orientative planar transition state. 

The photochemical synthesis of optically active oxaziridines from prochiral nitrones was driven by an interest in examining the configurational stability of the oxaziridin nitrogen atom. Nitrone 7 was irradiated at — 78°C in a 1 1 mixture of ( + )- or (— )-2,2,2-trifluorophenylethanol (8) and fhiorotrichloromethane yielding nitrone 9lent-9 in 30% ee (absolute stereochemistry unknown) [17,18]. At room temperature this selectivity decreased to 5% ee. Less bulky residues also reduced the selectivity. An exchange of f-butyl by /-propyl led to 20% ee at — 78°C (Scheme 5). 

Enders and coworicers have shown that deprotonation of chiral SAMP/RAMP hydrazones (or their substituted analogs) derived from ketones or aldehydes, followed by reaction with Davis oxaziridine reagent provides the a-hydroxy hydrazones in moderate yield but with high diastereoselectivity. Direct unmasking or protection followed by unmasking provides the corresponding a-hydroxy ketones or aldehydes respectively (Scheme 24). Both antipodes of the hydroxylated compounds are available by appropriate choice of (5)- or (R)-proline-deiived auxiliaries. The direction of induction is predictable, if not wholly uniform (R substitution alters the a-stereochemistry for aldehyde hydrazones). The process clearly provides a valuable approach to both systems. 

More recently, Usuki etal. studied, using NMR techniques, the conformation of spirocyclic oxaziridines 3 derived from substituted cyclohexanones <1995JOC8028>. Depending on substitution and on the stereochemistry, these compounds exhibit a substantial upfield shift of the cyclohexyl methylene or methane protons with a 1,3-diaxial relationship to the oxaziridine N-substituent. This effect is ascribed to a conformation that places an aromatic group over the plane of the cyclohexane ring. This conformation has also been observed in the solid state by X-ray crystallography and is further supported by molecular mechanics calculations. 

Treatment of the laterally lithiated amide generated from lactam 273 with LDA with /ra r-2-phenylsulfonyl-3-phenyloxaziridine 33 afforded hydroxyl product 274 in 85% yield as a single isomer <1999JOC8627>. Use of (+)-(camphorsulfonyl)oxaziridine 202 gave similar results. The /ra t-stereoselectivity is consistent with the earlier finding that the hydroxylation stereochemistry is controlled by nonbonded steric interactions in the transition state such that the oxygen of the oxaziridine is delivered from the sterically least hindered direction. Treatment of 275 with LDA followed by (+)-(camphorsulfonyl)oxaziridine 202 afforded hydroxyl product 276 in 47% yield and 60% ee <1997T8881>. 

The photochemical isomerization reaction has been shown" to be stereospecific following the disrotatory photochemically allowed cyclization path. Thus the stereochemistry of the nitrone is preserved in the oxaziridine. However, since some nitrones undergo trans-cis isomerization under the conditions of photolysis, mixtures of oxaziridines often result. 

The stereochemistry of the oxaziridine ring has received considerable attention mainly due to the chirality of the nitrogen atom and the appreciable barrier to its inversion thus, the separation of enantiomers became possible. Optically active oxaziridines have been prepared by the following methods ... 

The influ nee of reaction conditions on the stereochemistry of the oxidation of optically act ve or racemic Af-diphenylmethylene a-methylbenzylamines 40 with chiral or achiral peroxy acids to oxaziridines was investigated. It was found that asymmetric induction at the ring nitrogen in the resulting oxaziridine from optically active imine 40 does not depend on the nature of the peroxy acid or the solvent. However, the diastereoselectivity seems to be dependent only on the reaction temperature. The ratio of the resulting oxaziridine diastereomers changed by 10% when the reaction temperature was raised from — 30°C to -t-40°C. On the other hand, the enantioselectivity was found to depend on the chirality of the peroxy acid, the temperature, and the solvent. For example, the optical yield of the major oxaziridine diastereomer decreased from 3.4 to 1.3 when the solvent was changed from chloroform to methanol in the oxidation of racemic 40. 

This sequence has been used to convert a pyrroline ring to useful functional groups with control of stereochemistry. (This reaction is a variation of the oxidation of oxaziridines to nitroso compounds. )... 

During the highly stereoselective total synthesis of epothilone B by J.D. White and co-workers, the stereochemistry of the alcohol portion of the macrolactone was established by applying Davis oxaziridine oxidation of a sodium enolate. The sodium enolate was generated from the corresponding chiral oxazolidinone derivative, which upon oxidation gave 71% yield of a-hydroxylated compound. 

The first total synthesis of (-)-fumiquinazoline A and B was accomplished by B.B. Snider and co-workers using a Buchwald-Hartwig Pd-catalyzed cyclization of an iodoindole carbamate to construct the imidazoindolone moiety. In order to set up the stereochemistry at the benzylic position of the indole fragment, the double bond was oxidized with the saccharine-derived Davis oxaziridine in the presence of methanol to give the major diastereomer in 65% yield. 

The product stereochemistry for reagent-induced hydroxylations are under the control of a noncovalently bound chiral reagent which avoids the introduction and eventual removal of the chiral auxiliary as discussed in the preceding section. This method requires an enantiopure N-sulfonyloxaziridine of which (camphorylsulfonyl)oxaziridines (74), (114), and (158) have proven the most useful <92CRV919>. Both epimeric a-hydroxy carbonyl compounds are readily available because the antipodal oxidant controls the absolute stereochemistry of the product (Scheme 25). Oxaziridines (74) and (114) are commercially available. 

The JlT-ray crystal and molecular structure of the stable nitrogen pyramid of c/j-2-isopropyl-3-(4-nitrophenyl)oxaziridine (25) has confirmed its stereochemistry. A similar study of 1,2-diadamantylazetidinone shows that the... 

Several new methods for the preparation of olefins by deoxygenation of epoxides or desulphurization of episulphides have been reported. Mono-, di-, tri-, and tetra-substituted epoxides yield olefins (75—97%) when treated with lithium in refluxing THF (16— 98 h). Aliphatic epoxides give olefins with retention of stereochemistry, but JB-stilbene was produced from each isomer of the corresponding epoxide. Episulphides are reduced to olefins with better than 99% retention of configuration and in yields of 50—80% by 2-alkyl-oxaziridines. °... 

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