2-Sulfonyloxaziridines, preparation

Rosse et al. described the oxidation of the resin-bound /3-sulfenyl hydroxamic acids A -sulfonyloxaziridines <2001SL538>. For example, oxidation of 143 with 33 afforded the corresponding sulfoxide 144 in 71% yield after cleavage of the resin with TFA. Apfel et al. in the preparation of some potent peptide deformylase inhibitors and antibacterial agents employed a similar transformation<2000JME2324>. 

The transition state for oxygen transfer from iV-sulfonyloxaziridines to alkenes was studied by Anderson eta/, using the endocyclic restriction test <19990L1415>. In this study, molecules containing both the oxaziridine and alkene functionalities were prepared, and the ability of each system to intramolecularly transfer oxygen was evaluated. The results are consistent with a transition state in which N-0 bond cleavage is more advanced than C-O bond cleavage. 

Reaction of a mixture of unsaturated esters 271a and 271b with KHMDS followed by addition of A -sulfonyloxaziridine 33 gave a-hydroxy ester 272 in 72% yield <1995TL413>. The bromo analogue was prepared similarly in 78% yield. 

Garcia Ruano al. reported an important new procedure for the preparation of diverse A -sulfonyloxaziridines <2005OL5493>. This method involves the one-pot, two-step oxidation of readily available A -sulfmylimines 352 first with MCPBA followed by MCPBA/KOH to give the oxaziridines 353 in excellent yields (Table 29). 

Table 29 Preparation of N-sulfonyloxaziridines 353 from A/-sulfinylimines 352 <2005OL5493>...

The advantage that this procedure has over earlier methods is that A -sulfonyloxaziridines derived from aliphatic aldehydes and ketones can be prepared. 

The asymmetric hydroxylation of ester enolates with N-sulfonyloxaziridines has been less fully studied. Stereoselectivities are generally modest and less is known about the factors influencing the molecular recognition. For example, (/J)-methyl 2-hydroxy-3-phenylpropionate (10) is prepared in 85.5% ee by oxidizing the lithium enolate of methyl 3-phenylpropionate with (+)-( ) in the presence of HMPA (eq 13). Like esters, the hydroxylation of prochiral amide enolates with N-sulfonyloxaziridines affords the corresponding enantiomerically enriched a-hydroxy amides. Thus treatment of amide (11) with LDA followed by addition of (+)-( ) produces a-hydroxy amide (12) in 60% ee (eq 14). Improved stereoselectivities were achieved using double stereodifferentiation, e.g., the asymmetric oxidation of a chiral enolate. For example, oxidation of the lithium enolate of (13) with (—)-(1) (the matched pair) affords the a-hydroxy amide in 88-91% de (eq 15). (+)-(Camphorsulfonyl)oxaziridine (1) mediated hydroxylation of the enolate dianion of (/J)-(14) at —100 to —78 °C in the presence of 1.6 equiv of LiCl gave an 86 14 mixture of syn/anti-(15) (eq 16). The syn product is an intermediate for the C-13 side chain of taxol. 

Thiones (Ar2C=S) are oxidized to thiones 5-oxides (Ar2C=S=0) by A-sulfonyloxaziridine (78) (Scheme 14) <87JCS(Pl)l 113). The oxidation is fast and quantitative, exhibiting second-order kinetics. Thiocamphor 5-oxide (79) and thiofenchone 5-oxide (80) were prepared in 91% and 76% yield, respectively by oxidation of the corresponding thiones with (78b). Earlier attempts to prepare these materials with other oxidants resulted in low yields and the products were difficult to purify. Phosphorothionates (R2P(S)OPh) are oxidized to phosphates (R2P(0)0Ph) by A-sulfonyl-oxaziridines <88MI 112-01). 

The most widely used application of (V-sulfonyloxaziridines is for the synthesis of a-hydroxy carbonyl compounds (125), a key structural unit found in many biologically important molecules (Scheme 24). Compounds containing this array are also useful as chiral auxiliaries and as synthetic building blocks for asymmetric synthesis. Although a number of indirect methods have been devised to prepare a-hydroxy carbonyl compounds, the enolate oxidation protocol, using (V-sulfonyloxaziridines, is undoubtedly the most versatile because of the great diversity of metal enolate... 

Of particular concern with a-hydroxy carbonyl compounds is the stereochemistry of the hydroxy group attached to the stereogenic carbon because biological activity is often critically dependent on its orientation. A-Sulfonyloxaziridines have played a prominent role in the stereoselective synthesis of this key structural element (Scheme 25). Enantiomerically and diastereomerically enriched materials have been prepared by (1) the hydroxylation of chiral nonracemic enolates with racemic A-sulfonyloxaziridines, for example (63a) (2) the asymmetric hydroxylation of prochiral enolates with enantiopure A-sulfonyloxaziridines and (3) a combination of the first two, double stereodifferentiation. 

Starting with (5)-1 -phenylethyl amine, a chiral sulfonyloxaziridine has been prepared by A,T-sul-fonylation and subsequent formation of an imine with an aromatic aldehyde (best example pentafluorobenzaldehyde). Oxidation leads to a 1 1 mixture of diastereomeric oxaziridines 77 which can be separated by HPLC76. The compounds behave similarly to the chiral camphor-derived sulfonyloxaziridines, as they are able to epoxidize alkenes not containing special functional groups with some enantioselectivity (Section D.4.5.2.1.). Another attractive starting material is cheap commercial saccharin. Reaction with alkyl- or aryllithium compounds leads to addition... 

Chiral N-sulfonyloxaziridines are useful reagents for the asymmetric synthesis of sulfoxides, selenoxides, and other substrates. Davis and co-workers <97JOC3625> have reported the first example of an e.vtt-camphorylsulfonyloxaziridine 175. prepared by the MCPBA oxidation of camphor inline 174 in the presence of potassium hexamethyldisilazide. This compound was then studied in various asymmetric oxidation applications. 

The very useful A-sulfonyloxaziridines are conveniently prepared by treating A-sulfonylimines with Oxone in a biphasic solvent system (eq 18). Either bicarbonate or carbonate can be used to buffer this reaction, but reaction is much faster with carbonate, suggesting that the monopersulfate dianion is the oxidizing species (for illustrations of the remarkable chemistry of these oxaziridines, see N-(Phenylsulfonyl)(3,3-dichlorocamphoryl)-oxaziridine). 

The novel highly optically active polysulfoxides (111) and (112) (276) with chiral sulfonyl groups in the main chain were prepared by asymmetric oxidation of corresponding polysulfides by using chiral A/-sulfonyloxaziridine. The polysulfoxide with the enantiomeric excess (ee) of up to 91% was obtained in good chemoselectivity when the reaction was carried out with one equivalent of (—)-iV-sulfonyloxaziridine (113) in chloroform at room temperature followed by reflux. 

Amine N-oxides can be prepared from amines with 30% aqueous hydrogen peroxide in a non-catalytic slow reaction (80, 90]. At elevated temperatures this oxidation proceeds at a reasonable rate and has been used in industrial applications. Various other oxidants have also been employed for N-oxidation of tertiary amines such as peracids [91], 2-sulfonyloxaziridines [92] and a-azohydroperoxides [93]. 

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