Dichloro oxaziridine

Modest to low ees are reported for the oxaziridine mediate asymmetric hydroxylation of 4,5-dihydroisoxazoles (177) to 4,5-dihydro-4-isoxazolols (178) (Equation (42)) <93JOC759i>. Dichloro oxaziridine (+)-(74) and the lithium enolate, generated in the presence of TMEDA, gave the best results. Transition state TS-2 predicts the absolute configuration of the product which was confirmed by chemical correlation. 

In the syntheses of (-)-lepadins A, B, and C, which exhibit strong cytotoxicity against human cancer cells, enolate oxidation relied on the chiral, nonracemic dichloro oxaziridine 6 to deliver the product 57 in a stereoselective manner.46 Studies on this reaction demonstrated a higher stereoselectivity for the lithium enolate in comparison to a similarly generated sodium enolate. Their results also indicated that the reaction between 56 and 6 constituted a stereochemically matched case, whereas the use of racemic oxaziridine reagent 1 as well as use of the alternate enantiomer of 6 resulted in greatly reduced diastereoselectivity. 

R,8aR )-[(8,8-DIMETHOXY-CAMPHORYL)SULFONYL]OXAZIRIDINE AND (+)-(2R,8aR )-[(8l8-DICHLORO-CAMPHORYL)SULFONYL]-OXAZIRIDINE... 

For the preparation of (R)-C-6 sulfoxytetrahydromevinic acid lactone (73), a precursor of a potent HMG-CoA reductase inhibitor, optimal results were obtained with (—)-[(8,8-dichloro-camphoryl)sulfonyl]oxaziridine (74) <94TL346l>. 

The (camphorsulfonyl)oxaziridine derivatives, for example (74), generally give lower ees for the asymmetric oxidation of sulfides to sulfoxides than A-(phenylsulfonyl)(3,3-dichloro-camphoryl)oxaziridine (69) <88JA8477,88JCS(P1)1753,92JOC7274). 

Perfluoro-c -2,3-dialkyloxaziridines (64) are prepared in good yield (68-77%) by MCPBA oxidation of the corresponding perfluoroazaalkenes (188) (Equation (46)) <93JOC4754>. To be successful, the peracid needs to be > 80% pure, well-dried, and the solvent needs to be acetonitrile. Interestingly, oxidation does not proceed in CH2C12. A series of 3-/-butyl-3-( 1 -haloalkyl)oxaziridine were prepared by oxidation of the corresponding a-chloro, a-bromo, a,a-dichloro, and a,a-dibromo aldimines with MCPBA <92T7345>. 

Synthesis of (+)-(2R,8aS)-((8,8-Dimethoxycamphory()-sulfonyl]oxaziridine and (+)-(2R,8a)-[(8,8-Dichloro-camphoryl)sulfonyl]oxaziridine. 

Finally, Schmidt and coworkers have similarly applied the hydroxylation of phosphonates for synthesis of some sialyltransferase inhibitors. Thus, the stabilized enolate of 71 was selectively oxidized using dichloro(camphorsulphonyl)oxaziridine (6) to produce the a-hydroxy diallylphosphonate in low yield but as a single stereoisomer. The reaction was also found to be effective for compounds containing a variety of ring substituents.59,60... 

Enantioselective Oxidation with (Camphorsulfonyl) Oxazi-ridines. The synthesis of 2-substituted-2-hydroxy-l-tetralones from 2-substituted- 1-tetralone sodium enolates, obtained from the corresponding ketones and NaHMDS, proceeded with high enan-tioselectivities in the presence of (+)-(2i ,8ai )-[(8,8-dichloro-camphoryl)sulfonyl]oxaziridine (eq 24). ... 

Preparative Methods the (—)-oxaziridine (1) is prepared from (17 )-(+)-camphor by condensation with benzenesulfonamide/ TiCU (eq 1). The chlorine atoms are introduced via the sulfonimine azaenolate by treatment with sodium hex-amethyldisilazide and A -chlorosuccinimide or preferably with l,8-diazabicyclo[5.4.0]undec-7-eneand l,3-dichloro-5,5-dimethylhydantoin. Although oxidation of the dichlorosul-fonimine (2) requires >95% m-chloroperbenzoic acid and 4-5 days for completion, the oxidation can be carried out on a multigram scale (>60g). Higher yields of (1) are obtained when (2) is dissolved in a minimum of the CH2CI2 solvent. The antipode, (+)-( ), is similarly availablefrom(l5)-(-)-camphor. 

In 1995, Page reported asymmetric sulfoxidation using [(3,3-methoxycamphoryl) sulfonyl] oxaziridine 61, and the corresponding imine 62, as well as the dichloro derivative 63 and 64 (Fig. 1.13) [121]. 64 has been shown to be the most selective in previous studies, and can be used to prepare aryl alkyl sulfoxides in greater than 95% ee. 

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