Chiral A -sulfonyloxaziridines

Asymmetric Oxidation of Sulfides. Prochiral sulfides are oxidized by (camphorylsulfonyl)oxaziridine (1) to optically active sulfoxides. Over-oxidation to sulfones is not observed (eq 1 ). However, the best chiral A-sulfonyloxaziridines for the asymmetric oxidation of sulfides to sulfoxides are the (+)- and (Phenylsulfonyl )(3,3-dichlorocamphoryl )oxazi ridinesfi... 

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. 

Asymmetric sulfide oxidations are reported using oxaziridines other than A -sulfonyloxaziridines, but it is necessary to use a protic acid or Lewis acid to increase their reactivity. For example, -tolyl methyl sulfide 152 with bicyclic oxaziridine 153 in the presence of TFA gave the (A)-sulfoxide 154 in 50% yield and 42% ee in 24 h <1999T155>. It is interesting to note that use of MsOH resulted in much faster reaction with the oxidation complete in less than a minute. Similarly, sulfide 155 with chiral oxaziridine 156 in the presence of zinc chloride afforded sulfoxide 157 in 30% yield and 55% ee <2005JOC301>. 

The organocatalytic asymmetric a-hydroxylation of ketones with A -sulfonyloxaziridines was studied by Engqvist et al. <2005TL2053>. For example, the direct diamine-catalyzed enantioselective a-hydroxylation of ketones 255 with 7ra S -2-/>-tolylsulfonyl-3-phenyloxaziridine 33 in the presence of chiral diamine 256 afforded the corresponding a-hydroxylated products 257 in moderate yields with up to 63% ee. 

Davis, F. A., Billmers, J. M. Chemistry of oxaziridines. 5. Kinetic resolution of sulfoxides using chiral 2-sulfonyloxaziridines. J. Org. Chem. 

Poly(ester 0-sulfide)s Il-m were oxidized by using stoichiometric amounts of the chiral 2-sulfonyloxaziridine 1 to give chiral po1y(ester 0-sulfoxide)s V-m in nearly a quantitative yield, according to Scheme 1. The IR and NMR spectra and elemental... 

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. 

The utility of oxaziridines in asymmetric a-hydroxylation also extends to reactions with achiral enolates. This has been made possible by the discovery that certain chiral A -sulfonyl oxaziridines can react with enolates to afford a-hydroxy carbon compounds in excellent yield and enantioselectivity. An application of a highly selective sulfonyloxaziridine derived from camphor to the synthesis of daunomycin is shown in Scheme 8.23. Attack of the oxaziridine presumably occurs such that the enolate ester avoids nonbonded interactions with the exo methoxy group on the bicyclic ring system (cf. Schemes 8.23c and d). This is a very useful reaction of wide scope, and can be carried out on both stabilized enolates derived from keto esters (shown) and simple ketone enolates [99]. 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Oxidation of chiral sulfonimines (R"S02N=CHAr)and chiral sulfamyl-imines (R RNS02N=CHAr)affords optically active 2-sulfonyloxaziridines and 2-sulfamyloxaziridines, respectively. These chiral, oxidizing reagents have been used in the asymmetric oxidation of sulfides to sulfoxides (15-68% ee), 11-13 selenides to selenoxides (8-9% ee] enolates to a-hydroxycarbonyl compounds (8-37% ee) and in the asymmetric epoxidation of alkenes (15-40% ee)... 

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. 

Highly acid sensitive a-siloxy epoxides (108 R1 = R2 = Me) are available in good to excellent yields through the epoxidation of silyl enols ethers (107) with jV-sulfonyloxaziridine (63b) <87JOC954>. Hydrolysis of (108) gave the a-hydroxy carbonyl compound (109) in good-to-excellent yield (55-95%) and represents an alternative to peracids usually used to effect this transformation known as the Rubottom reaction. With chiral nonracemic TV-sulfonyloxaziridines the ees of (109) were low (7-11% ee) because of the poor facial discrimination between the re and si faces of the silyl enol ether (Scheme 20). 

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... 

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. 

Chiral sulfonyloxaziridines as oxidants in a-hydroxylation of /i-dicarbonyl compounds 04MI39. 

The 2-sulfonyloxaziridine (57) is a more selective oxidant than peracids. The reagent has been employed in the oxidation of sulfides to sulfoxides, disulfides to thiolsulfinates, selenides to selenoxides, thiols to sulfenic acids, organometallic reagents to alcohols and phenols, ketone and ester enolates to a-hydroxycarbonyl compounds (equation 31)41. The oxidation of chiral amide enolates gives optically active a-hydroxy carboxylic acids with 93-99% enantiomeric excess42. 

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... 

Davis et al. have developed a useful class of chiral oxidants based on N-sulfonyloxaziridines derived from camphor (for a review, see ref. [40]). Compounds (28) and (29) are the most efficient reagents [41,42]. Representative results are listed in Table 1.1. 

---