(±)-trans-2-(Phenylsulfonyl)-3-phenyloxaziridine1

[63160-13-4]  · C13H11NO3S  · (±)-trans-2-(Phenylsulfonyl)-3-phenyloxaziridine  · (MW 261.32)

(neutral, aprotic, electrophilic oxidizing agent for the chemoselective oxidation of many nucleophilic substrates1)

Physical Data: mp 95-95.5 °C.

Solubility: sol CH2Cl2, CHCl3, THF; insol hexane, pentane, water.

Form Supplied in: white solid.

Analysis of Reagent Purity: 1H NMR analysis and mp determination.

Preparative Methods: the title reagent (1) can be readily prepared on a 100 g scale in 88% yield via oxidation of N-benzylidenebenzenesulfonamide with buffered m-Chloroperbenzoic Acid2 or more conveniently with Potassium Monoperoxysulfate (Oxone).3 This Baeyer-Villiger type of oxidation of sulfonimine affords only the trans-oxaziridine. A number of other (±)-trans-2-(arylsulfonyl)-3-aryloxaziridines (2) can also be prepared by these methods.2,3

Purification: recrystallization from ethyl acetate-pentane.2

Handling, Storage, and Precautions: can be stored in a brown bottle in the refrigerator for years without noticeable decomposition. Storage at rt for long periods of time, however, is potentially hazardous.2 The nitro-substituted oxaziridines (2) are more thermally stable and are recommended for reactions at elevated temperatures.

Oxidation of Organosulfur Compounds.

(±)-trans-2-(Arylsulfonyl)-3-aryloxaziridines oxidize a variety of sulfides to sulfoxides without over-oxidation to sulfones, even in the presence of excess oxidant.1a,4 However, longer reaction times (>20 h) can produce sulfones.4 An example is the oxidation of mustard to the sulfoxide in less than 2 min by trans-2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine (2a) (eq 1).5 In contrast to m-CPBA or Oxone, oxaziridine-mediated oxidation of alkynyl phenyl sulfides at 60 °C gives none of the corresponding sulfone (eq 2).6 The oxidation of sulfides has been developed in a catalytic manner.7 Disulfides are usually oxidized to thiosulfinates which are difficult to obtain using acidic oxidants such as m-CPBA (eq 3).8 Enantiopure N-sulfonyloxaziridines afford enantiomerically enriched sulfoxides and thiosulfinates.9

Thiols are oxidized to sulfenic acids (3) which can then be trapped by alkynes to give vinyl sulfoxides (4). In the absence of the trapping agent, the initial sulfenic acid (3) is usually further oxidized to a sulfinic acid (5) due to the a-effect (eq 4).10 2-Mercaptopyridine, however, gives rise to the disulfide (eq 5).11 Silyl sulfides (silyl ether of thiols), afford silyl sulfinates regardless of the stoichiometry of the reaction (eq 6).12 Oxidation of thiones gives thione S-oxides which may undergo desulfurization to ketones (eq 7).13 By the oxidation of the corresponding thiones with oxaziridine (2b), thiocamphor S-oxide (6) and thiofenchone S-oxide (7) are prepared in 91% and 76% yield, respectively.13 Reaction of phosphorothionate with (2a) yields the phosphate (eq 8).14

Oxidation of Organoselenium Compounds.

Selenides, like sulfides, are quantitatively oxidized to selenoxides without overoxidation.1a,15 The resulting selenoxides may undergo [2,3]-sigmatropic rearrangement to allylic alcohols or b-elimination to alkenes (eq 9).1a,16 The reaction can be run in the presence of a number of other functional groups such as aldehyde,17 alkene,18 and sulfide.16 Compared to Hydrogen Peroxide or m-CPBA, improved yields are reported using oxaziridine (2a).19 Oxaziridine-mediated selenide oxidations in the presence of pyridine have been used to suppress side products of the selenoxide elimination.15 Diphenyl diselenide gives benzeneseleninic anhydride (eq 10).17

Oxidation of Organonitrogen and Organophosphorus Compounds.

Tertiary amines react with (1) to yield amine oxides (eq 11).1a,20 Oxidation of secondary amines with one equiv of (1) affords the hydroxylamine (eq 12),21 while excess oxaziridine gives rise to nitrones.20 Aliphatic primary amines give, on oxidation, nitroso compounds (eq 13).20 Although pyridine is not reactive towards oxaziridines,20 imines are oxidized to nitrones (eq 14).22 With (2b), 1,3,2-l3-oxazaphospholanes gave 1,3,2-l5-oxazaphospholanes (eq 15).23

Oxidation of Carbon-Carbon Double Bonds and Aromatic Hydrocarbons.

Like peroxy acids, N-sulfonyloxaziridines epoxidize alkenes in a syn stereospecific manner, but the epoxidation is slower requiring higher temperature (e.g. 60 °C) for satisfactory yields.1a,24 For this reason, the more thermally stable p-nitrophenyl oxaziridine (2a) is recommended. The neutral and aprotic N-sulfonyloxaziridine oxidizing reagents can be used to prepare acid-sensitive epoxides. For example, epoxidation of indene with (2a) gave the acid-sensitive indene oxide in 63% yield (eq 16).24 Usually, electron-deficient alkenes are not epoxidized by N-sulfonyloxaziridines; however, isoxazoline (8) gave epoxides (9) and (10) in 36% yield on heating with (2a) (eq 17).25 In general, more nucleophilic substrates such as sulfides, amines, selenides, etc., can be oxidized in the presence of C=C double bonds (e.g. eq 2). Alkynes, on the other hand, are not oxidized by N-sulfonyloxaziridines such as (2).

Oxidation of silyl enol ethers followed by acid hydrolysis gives a-hydroxy carbonyl compounds.1a,26 The aprotic nature of N-sulfonyloxaziridines makes possible the isolation of the a-siloxy epoxide intermediate in high yield (eq 18).26 a-Hydroxy ketones of high enantiomeric purity (&egt;98% ee) can be prepared via the oxidation of chiral silyl enol ethers (eq 19).27

Disubstituted enamines are rapidly oxidized to a-amino ketones, while tertiary enamines give, after hydrolysis, a-hydroxy ketones (eq 20).1a,28 Oxidation of bicyclic enamines with (1) followed by reduction of the iminium ion with Sodium Borohydride affords the b-amino alcohol (eq 21).29 Reaction of diene carboxylic acid with oxaziridine (1) is reported to give a diastereomeric mixture of hydroxy lactones (eq 22).30 Heating anisole with N-sulfonyloxaziridine (2a) gives a mixture of 2- and 4-methoxyphenols.31

Oxidation of Carbanions and Organometallic Compounds.

Lithium and Grignard (RM) reagents react instantaneously with N-sulfonyloxaziridines to give alcohols and phenols (eq 23).1a,32 Yields are comparable to those obtained using alternative oxidants such as O2, t-BuOOLi, Bis(trimethylsilyl) Peroxide, and Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) (MoOPH). The oxaziridine reagent is particularly recommended for substrates having certain sensitive functionality. Bishydroxylation is also possible with (1) (eq 24).33 Oxidation of phosphorus ylides (Wittig reagents) with (1) gives trans-alkenes or ketones depending on the structure of the phosphoranes (eq 25).34 Bis-ylides dimerize to cycloalkadienes.34 Reaction of dimethyloxosulfoniummethylide with (1) results in the formation of azetidines (eq 26).35 Unsymmetrical a-diketones are prepared in good yield by oxidation of the carbanions derived from a-sulfonyl ketones with oxaziridine (2c) (eq 27).36

2-(Arylsulfonyl)-3-aryloxaziridines oxidize a variety of metal enolates to the corresponding a-hydroxy carbonyl compounds (eq 28).1,37,38 Unlike MoOPH and molecular oxygen, over-oxidation is not a problem with these reagents.1,39 With chiral enolates, the oxidation takes place from the least hindered face of the enolate.1,40 a-Hydroxy ketones, aldehydes, and carboxylic acid derivatives of high enantiomeric purity are available using chiral auxiliaries (eqs 29 and 30).1,41,42


1. (a) Davis, F. A.; Sherppard, A. C. T 1989, 45, 5703. (b) Davis, F. A.; Chen, B.-C. CRV 1992, 92, 912.
2. Vishwakarma, L. C.; Stringer, O. D.; Davis, F. A. OS 1988, 66, 203.
3. Davis, F. A.; Chattopadhyay, S.; Towson, J. C.; Lal, S. G.; Reddy, T. JOC 1988, 53, 2087.
4. Davis, F. A.; Jenkins, Jr., R.; Yocklovich, S. G. TL 1978, 5171.
5. Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Davis, F. A. JOC 1990, 55, 3664.
6. Kabanyane, S. T.; MaGee, D. I. CJC 1992, 70, 2758.
7. Davis, F. A.; Lal, S. G.; Durst, H. D. JOC 1988, 53, 5004.
8. Davis, F. A.; Jenkins, Jr., R. H.; Yocklovich, S. G. TL 1978, 5171.
9. Davis, F. A.; Thimma Reddy, R.; Han, W.; Carroll, P. J. JACS 1992, 114, 1428.
10. Davis, F. A.; Billmers, R. L. JACS 1981, 103, 7016.
11. Davis, F. A.; Jenkins, Jr., R. H. JACS 1980, 102, 7967.
12. Davis, F. A.; Rizvi, S. Q. A.; Ardecky, R.; Gosciniak, D. J.; Friedman, A. J.; Yocklovich, S. G. JOC 1980, 45, 1650.
13. Maccagnani, G.; Innocenti, A.; Zani, P.; Battaglia, A. JCS(P2) 1987, 1113.
14. Bielawski, J.; Casida, J. E. J. Agric. Food Chem. 1988, 36, 610.
15. Davis, F. A.; Stringer, O. D.; Billmers, J. M. TL 1983, 24, 1213.
16. Ley, S. V.; Somovilla, A. A.; Broughton, H. B.; Craig, D.; Slawin, A. M. Z.; Toogood, P. L.; Williams, D. J. T 1989, 45, 2143.
17. Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Pergamon: New York, 1986; p 127.
18. Diez-Martin, D. D.; Grice, P.; Kolb, H. C.; Ley, S. V.; Madin, A. TL 1990, 31, 3445.
19. Kolb, H. C.; Hoffmann, H. M. R. TA 1990, 1, 237.
20. Zajac, Jr., W. W.; Walters, T. R.; Darcy, M. G. JOC 1988, 53, 5856.
21. (a) Fukuyama, T.; Goto, S. TL 1989, 30, 6491. (b) Jasys, V. J.; Kelbaugh, P. R.; Nason, D. M.; Phillips, D.; Rosnack, K. J.; Saccomano, N. A.; Stroh, J. G.; Volkmann, R. A. JACS 1990, 112, 6696.
22. Milliet, P.; Lusinchi, X. TL 1985, 26, 3791.
23. Stumpf, R.; Lemmen, P. ZN(B) 1990, 45b, 1729.
24. Davis, F. A.; Abdul-Malik, N. F.; Awad, S. B.; Harakal, M. E. TL 1981, 22, 917.
25. Wade, P. A.; Bereznak, J. F.; Palfey, B. A.; Carroll, P. J.; Dailey, W. P.; Sivasubramanian, S. JOC 1990, 55, 3045.
26. Davis, F. A.; Sheppard, A. C. JOC 1987, 52, 954.
27. Lohray, B. B.; Enders, D. HCA 1989, 72, 980.
28. Davis, F. A.; Sheppard, A. C. TL 1988, 29, 4365.
29. Heidt, P. C.; Bergmeier, S. C.; Pearson, W. H. TL 1990, 31, 5441.
30. Berlage, U.; Schmidt, J.; Peters, U.; Welzel, P. TL 1987, 28, 3091.
31. Davis, F. A.; Abdul-Malik, N. F.; Jenkins, L. A. JOC 1983, 48, 5128.
32. (a) Davis, F. A.; Mancinelli, P. A.; Balasubraminian, K.; Nadir, U. K. JACS 1979, 101, 1044. (b) Davis, F. A.; Wei, J.; Sheppard, A. C.; Gubernick, S. TL 1987, 28, 5115.
33. Hasseberg, H.-A.; Gerlach, H. HCA 1988, 71, 957.
34. Davis, F. A.; Chen, B.-C. JOC 1990, 55, 360.
35. Nadir, U. K.; Sharma, R. L.; Koul, V. K. IJC(B) 1989, 28B, 685.
36. Williams, D. R.; Robinson, L. A.; Amato, G. S. Osterhout, M. H. JOC 1992, 57, 3740.
37. Davis, F. A.; Vishwakarma, L. C.; Billmers, J. M.; Finn, J. JOC 1984, 49, 3241.
38. Lee, K.-C.; Wu, J. C. C.; Yen, K.-F.; Uang, B.-J. TL 1990, 31, 3563.
39. Davis, F. A.; Chen, B.-C. MOC in press.
40. (a) Belletire, J. L.; Ho, D. M.; Fry, D. F. J. Nat. Products 1990, 53, 1587.
41. Enders, D.; Bhushan, V. TL 1988, 29, 2437.
42. Evans, D. A.; Morrissey, M. M.; Dorow, R. L. JACS 1985, 107, 4346.

Bang-Chi Chen

Bristol-Myers Squibb Company, Syracuse, NY, USA

Franklin A. Davis

Drexel University, Philadelphia, PA, USA



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