N-(Phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine1

(-)

[22270-28-4]  · C16H19Cl2NO3S  · N-(Phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine  · (MW 376.33) (+)

[138874-52-9]

(asymmetric oxidizing reagent for the enantioselective oxidation of sulfides to sulfoxides,1 selenides to selenoxides,2 and sulfenimines to sulfinimines3)

Physical Data: mp 121-122 °C; (3S,2R)-(-) [a]20D -159° (c 4.2, CHCl3); (3R,2S)-(+) [a]20D +157° (c 4.1, CHCl3).

Solubility: insol H2O; sol CH2Cl2, CHCl3, THF, alcohols; sparingly sol CCl4.

Form Supplied in: white solid.

Analysis of Reagent Purity: by mp and specific rotation determination.

Preparative Methods: the (-)-oxaziridine (1) is prepared from (1R)-(+)-camphor by condensation with benzenesulfonamide/TiCl4 (eq 1). The chlorine atoms are introduced via the sulfonimine azaenolate by treatment with Sodium Hexamethyldisilazide and N-Chlorosuccinimide or preferably with 1,8-Diazabicyclo[5.4.0]undec-7-ene and 1,3-dichloro-5,5-dimethylhydantoin.4,5 Although oxidation of the dichlorosulfonimine (2) requires >95% m-Chloroperbenzoic Acid and 4-5 days for completion, the oxidation can be carried out on a multigram scale (>60 g). Higher yields of (1) are obtained when (2) is dissolved in a minimum of the CH2Cl2 solvent. The antipode, (+)-(1), is similarly available from (1S)-(-)-camphor.

In contrast to 2-(phenylsulfonyl)-3-phenyloxaziridine, this less reactive reagent does not epoxidize alkenes or oxidize amines to amine oxides.

Purification: flash chromatography.

Handling, Storage, and Precautions: store at room temperature.

Asymmetric Oxidation of Sulfides to Sulfoxides.

Enantiopure sulfoxides are important as auxiliaries in the asymmetric construction of C-C bonds.6 The reaction of an organometallic reagent with a diastereomerically pure (-)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate, the Andersen synthesis, is the method most often employed for the preparation of nonracemic sulfoxides.7,8 However, this methodology is limited in the synthesis of highly functionalized sulfoxides as well as certain dialkyl sulfoxides. Alternatively, enantiomerically enriched sulfoxides are available via the asymmetric oxidation of prochiral sulfides to sulfoxides using Kagan's modification of the Sharpless reagent, synthetically useful (>90% ee) only for aryl methyl sulfides (Ar-S-Me)9 or the more general N-sulfonyloxaziridines (1).1

The asymmetric oxidation of sulfides to the sulfoxides by (-)-(1) is carried out at rt in nonpolar solvents (eq 2). Oxidations are generally complete within 1-6 h, although sulfides having electron-withdrawing or sterically demanding groups may require up to 48 h for completion. In these examples, heating to ca. 65 °C increases the rate of oxidation without significantly lowering the ee value. The sulfoxides and the sulfonimines (2) are isolated by TLC in >90% yield, with the latter being recycled. The highest enantioselectivities are observed for oxidations in low dielectric solvents such as CCl4 and for those sulfides (RL-S-RS) where the difference in size of the RL and RS groups is large, e.g. RL = aryl or t-butyl and RS = CH2R. Both enantiomeric sulfoxides are available by choice of the appropriate reagent because the configuration of the oxaziridine three-membered ring controls the absolute stereochemistry of the product, e.g. (-)-(1) gives (S)-sulfoxides while (+)-(1) gives (R)-sulfoxides (eq 2). The molecular recognition is predictable in terms of minimization of nonbonded steric interactions in the transition state. Examples are given in Table 1.1,8c,10

Asymmetric oxidation of 2,3-epoxy sulfides with (-)-(1), double stereodifferentiation, gives 2,3-epoxy sulfoxide diastereoisomers (eq 3).11 Lower de values were observed for the other epoxy sulfide enantiomer. The modified Sharpless reagent gave better de values (5.1:1) with the methyl sulfides.

Asymmetric Oxidation of Selenides to Selenoxides.

The difficulty in preparing optically active selenoxides is that they are configurationally unstable, forming achiral hydrates, ArSe(OH)2R, with trace amounts of water.12 Enantioselective oxidation of alkyl aryl selenides by (-)-(1), because of its aprotic nature, gives the selenoxides in 91% to >95% ee (eq 4). Oxidations are carried out as before (eq 2) except that moisture and trace amounts of acids in the solvents need to be rigorously excluded. The optically active selenoxides (Ar = 2,4,6-triisopropylphenyl) can be isolated by chromatography on basic alumina, but with some racemization (85-87% ee).12

Asymmetric oxidation of allylic selenides gives allylic alcohols via a [2,3]-sigmatropic selenoxide-selenate rearrangement (eq 5).2 In both oxidations, eqs 4 and 5, the configuration at the selenoxide is that predicted based on the sulfoxide model.

Aryl vinyl selenides (3) are oxidized by (-)-(1) to selenoxide intermediates which undergo elimination to chiral allenic sulfones (eq 6).12 Somewhat better ee values were observed using the modified Sharpless reagent (up to 38% ee). Asymmetric oxidation of cyclohexyl selenides by oxaziridine (-)-(1) give axially chiral cyclohexylidene derivatives in up to 83% ee (eq 7).13

Asymmetric Oxidation of Sulfenimines to Sulfinimines.

Enantiopure sulfinimines are ammonia imine synthons useful in the asymmetric synthesis of amines and b-amino acid derivatives.3,14,15 Sulfinimines unavailable via the Andersen synthesis (R = H)14,15 are prepared by asymmetric oxidation of the sulfenimines, ArS-N=C(R)PhX, with (+)-(1) or (-)-(1) at -20 to 20 °C in CCl4 (eq 8).3 Crystallization improves the ee to >95%. The sulfoxide chiral recognition model correctly predicts the configuration of the product.


1. Davis, F. A.; Thimma Reddy, R.; Han, W.; Carroll, P. J. JACS 1992, 114, 1428.
2. Davis, F. A.; Thimma Reddy, R. JOC 1992, 57, 2599.
3. Davis, F. A.; Thimma Reddy, R.; Reddy, R. E. JOC 1992, 57, 6387.
4. Davis, F. A.; Thimma Reddy, R.; Han, W.; Reddy, R. E. PAC 1993, 65, 633.
5. Mergelsberg, I.; Gala, D.; Scherer, D.; DiBenedetto, D.; Tanner, M. TL 1992, 33, 161.
6. For reviews on the synthesis and application of chiral sulfoxides, see: (a) Posner, G. H. In The Chemistry of Sulphones and Sulphoxides; Patai, S.; Rappoport Z.; Stirling, C. J. M., Eds.; Wiley: Chichester, 1988; Chapter 16, pp 823-849. (b) Posner, G. H. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: New York, 1983; Vol. 2, Chapter 8, pp 225-240. (c) Barbachyn, M. R.; Johnson, C. R. In Asymmetric Synthesis; Morrison, J. D.; Scott, J. W., Eds.; Academic: New York, 1983; Vol. 4, Chapter 2; pp 227-256. (d) Solladié, G. S 1981, 185.
7. Andersen, K. K. In The Chemistry of Sulphones and Sulphoxides; Patai, S.; Rappoport, Z.; Stirling, C. J. M., Eds.; Wiley: Chichester, 1988; Chapter 3, pp 55-94.
8. (a) Rebiere, F.; Samuel, O.; Ricard, L.; Kagan, H. B. JOC 1991, 56, 5991. (b) Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy, J.; Cherry, D. JACS 1992, 114, 5977. (c) Marino, J. P.; Bogdan, S.; Kimura, K. JACS 1992, 114, 5566.
9. Zhao, S. H.; Samuel, O.; Kagan, H. B. T 1987, 43, 5135 and references cited therein.
10. Rossi, C.; Fauve, A.; Madesclaire, M.; Roche, D.; Davis, F. A.; Thimma Reddy, R. TA 1992, 3, 629.
11. Rayner, C. M.; Sin, M. S.; Westwell, A. D. TL 1992, 33, 7237.
12. Komatsu, N.; Murakami, T.; Nishibayashi, Y.; Sugita, T.; Uemura, S. JOC 1993, 58, 3697.
13. Komatsu, N.; Matsunaga, S.; Sugita, T.; Uemura, S. JACS 1993, 115, 5847.
14. Annunziata, R.; Cinquini, M.; Cozzi, F. JCS(P1) 1982, 339.
15. Hua, D. H.; Miao, S. W.; Chen, J. S.; Iguchi, S. JOC 1991, 56, 4.

Franklin A. Davis

Drexel University, Philadelphia, PA, USA



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