Oxaziridines optically active

X-ray analysis of an optically active oxaziridine substituted at nitrogen with the 1-phenylethyl group of known configuration led to the absolute configuration (+)-(2R,3R)-2-(5-l-phenylethyl)-3-(p-bromophenyl)oxaziridine of the dextrorotatory compound as expected, C-aryl and A-alkyl groups were trans to each other (79MI50800). 

Also due to the high barrier of inversion, optically active oxaziridines are stable and were prepared repeatedly. To avoid additional centres of asymmetry in the molecule, symmetrical ketones were used as starting materials and converted to oxaziridines by optically active peroxyacids via their ketimines (69CC1086, 69JCS(C)2648). In optically active oxaziridines, made from benzophenone, cyclohexanone and adamantanone, the order of magnitude of the inversion barriers was determined by racemization experiments and was found to be identical with former results of NMR study. Inversion barriers of 128-132 kJ moF were found in the A-isopropyl compounds of the ketones mentioned inversion barriers of the A-t-butyl compounds lie markedly lower (104-110 kJ moF ). Thus, the A-t-butyloxaziridine derived from adamantanone loses half of its chirality within 2.3 days at 20 C (73JCS(P2)1575). 

NMR investigations in the diaziridine field also led to the problem of inversion stability at nitrogen. Further investigations paralleled those of oxaziridines NMR investigation in solution (67CB1178) was followed by preparative separation of invertomers and finally preparation of optically active individuals. 

The earliest attempts to obtain optically active sulfoxides by the oxidation of sulfides using oxidants such as chiral peracids did not fare well. The enantiomeric purities obtained were very low. Biological oxidants offered great improvement in a few cases, but not in others. Lately, some very encouraging progress has been made using chiral oxaziridines and peroxometal complexes as oxidants. Newer developments in the use of both chemical oxidants and biological oxidants are described below. 

Oxathiane dioxides lithiated 641 synthesis of 638, 647 Oxathiane oxides, synthesis of 352 Oxathiolane oxides, synthesis of 241 Oxaziridines 72, 254, 826 as optically active oxidizing agents 291 Oxazolidinones 826 Oxazolines 619, 788... 

En gros, the N insertion reactions can be subdivided into a Beckmann type and a Schmidt-type rearrangement part. Furthermore, some photochemical rearrangements of chiral oxaziridines are known to generate a range of optically active lactams. 

Optically active oxaziridines are useful reagents for the enantioselective oxidation of olefins 37 39). The following three preparative methods to make this reagent available have been reported enantioselective oxidation of an imine by (-)-peroxycam-phoric acid 37,38), photocyclization of a nitrone which has a chiral substituent39), and photocyclization of a nitrone in an optically active solvent 39). However, an... 

The 1 1 inclusion complexes 68 composed of 2a and nitrones 67 were prepared by keeping a solution of 2a and an equimolar amount of 67 in benzene-hexane (1 1) at room temperature for 12 h 40). Melting points of the complexes 68 are shown in Table 8. Irradiation of 68 in the solid state gave optically active oxaziridines 69. Irradiation time, yields and optical purity of the products are summarized in Table 8 40). Enantioselectivity in the formation of 67d, 67f, and 67g is high, but that of 69b, 69 c, and 69 e is low. This suggests a distinct influence coming from the substituents. 

Figure 6B.2. Transition-state models for epoxidation with optically active oxaziridines and dioxiranes.

The use of the optically active (camphorylsulphonyl)oxaziridine did not afford enantioselectivity. A possible explanation for this lack of stereocontrol lies in the mechanism proposed (Scheme 56). It involves formation of an a-amino epoxide, its nucleophilic ring opening and either loss of a proton (route a) or hydrolysis (route b) (Scheme 56). 

The photochemical synthesis of optically active oxaziridines from prochiral nitrones was driven by an interest in examining the configurational stability of the oxaziridin nitrogen atom. Nitrone 7 was irradiated at — 78°C in a 1 1 mixture of ( + )- or (— )-2,2,2-trifluorophenylethanol (8) and fhiorotrichloromethane yielding nitrone 9lent-9 in 30% ee (absolute stereochemistry unknown) [17,18]. At room temperature this selectivity decreased to 5% ee. Less bulky residues also reduced the selectivity. An exchange of f-butyl by /-propyl led to 20% ee at — 78°C (Scheme 5). 

Until quite recently the isolation of optically active seienoxides has been limited to those contained in steroids (isolated as diastereoisomeis). < The difficulty in obtaining these compounds was attributed to the racemization through the achiral hydrated intermediates. Simple optically active sel enoxides (S-11% ee) were first prepared by kinetic resolution. Direct oxidation of selenides to seienoxides was first reported using optically active oxaziridine derivatives under anhydrous conditions, but the extent of the asymmetric induction was somewhat unsatisfactory with methyl phenyl selenide as substrate (8-9% Recently much improved enantiomeric excesses (45-73%) were achieved with new oxaziridine reagents such as (70). An attempt at the asymmetric oxidation of more bulky selenides was independently carried out using Bu OCl in the presence of (-)-2-octanol (equation 55), but resulted in unsatisfactory enantioselectivities (ee 1%). Much better results were obtained by the oxidation of p-oxyalkyl aryl selenides (ee 18-40% equation 56) 27 gjyj selenides (ee 1-28%) using... 

The Grignard reagent 245 generated by treatment of optically active a-chlorosulfoxide 244 with ethylmagnesium chloride is hydroxylated by oxaziridine 33 to give secondary alcohol 246. The product was obtained in 80% yield and 91% ee <2000AGE3072>. 

Treatment of imine 331 with KHSOs (Oxone) in the presence of NaHC03 afforded A -alkyl oxaziridines 332 in 67-85% yields (Table 26) <2005JOC301>. Optically active oxaziridines of this type could be obtained using phenyl ethylamine as the chiral directing group (Table 26, entries 3 and 4). 

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 stereochemistry of the oxaziridine ring has received considerable attention mainly due to the chirality of the nitrogen atom and the appreciable barrier to its inversion thus, the separation of enantiomers became possible. Optically active oxaziridines have been prepared by the following methods ... 

Although partial resolution of 2- -propyl-3-methyl-3-isobutyloxaziridine (14, Wd = 3.94°) was reported in 1957, the first direct preparation of optically active oxaziridines was achieved in 1968. Treatment of a number of imines (Table 1 — entries 1, 2, 95, 96, 98, 100, 102) with (S)-(+)-monopercamphoric acid at 3°C in dichloromethane gave optically active oxaziridines in 47-80% yields. The optical purity of these oxaziridines was not established, but oxaziridine 14 was obtained with higher optical activity ([a]o = — 9.0°) than the sample obtained from partial resolution ([o ]d = — 3.94°). 

In the same year, an optically active oxaziridine with nitrogen as the only chiral center was prepared by the treatment of A -diphenylmethylenemethylamine 15 with (S)-(+)-monopercamphoric acid, (S)-(+)-2-(a-naphthyl)peroxypropionic acid, (R> (—)-2-phenylperoxypropionic acid, and (S)-(+)-2-methyiperoxybutyric acid to give 2-methyl-3,3-diphenyloxaziridine with optical rotations of [a] = — 49.2°, — 8.5°, + 12.5°, and — 5.7°, respectively. ... 

Further studies of asymmetric induction in the synthesis of optically active oxaziridines via oxidation of imines with chiral acids and the degree of stereoselectivity of these reactions have been reported. It was found that the degree of stereoselectivity in the conversion of aldimines and ketimines to oxaziridines by (+)-monopercamphoric acid (MPCA) is dependent on the solvent and the reaction temperature (Tables 4 and 5). The stereoselectivity of the reaction does not seem to depend on the nature of the alkyl group attached to nitrogen. ... 

Among the methods discussed in this section, the preparation of optically active oxaziridines using chiral peroxy acids has been employed extensively >51,52,54,60,633,66,72,73... 

The influ nee of reaction conditions on the stereochemistry of the oxidation of optically act ve or racemic Af-diphenylmethylene a-methylbenzylamines 40 with chiral or achiral peroxy acids to oxaziridines was investigated. It was found that asymmetric induction at the ring nitrogen in the resulting oxaziridine from optically active imine 40 does not depend on the nature of the peroxy acid or the solvent. However, the diastereoselectivity seems to be dependent only on the reaction temperature. The ratio of the resulting oxaziridine diastereomers changed by 10% when the reaction temperature was raised from — 30°C to -t-40°C. On the other hand, the enantioselectivity was found to depend on the chirality of the peroxy acid, the temperature, and the solvent. For example, the optical yield of the major oxaziridine diastereomer decreased from 3.4 to 1.3 when the solvent was changed from chloroform to methanol in the oxidation of racemic 40. 

A number of optically active oxaziridines have been synthesized by the photolysis of the corresponding nitrones in (+) or (—)2,2,2-trifluoro-l-phenylethanol/ fluorotrichloromethane as solvents (Table 6). ... 

A similar study using w-chloroperbenzoic acid to oxidize iminesin chiral alcohols gave optically active oxaziridines though in low optical purity (Table 7). It appears that the optical yield is dependent on the nature of the chiral solvent, the highest yield being in chiral alcohols with aromatic substituents. Recently, greater success has been achieved. ... 

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