Oxaziridines imine oxidation

It is noteworthy that quick and effective formation of diaryl nitrones can be achieved through oxidation of diaryl imines with Oxone (potassium peroxy-monosulfate) in such media as aqueous solution of NaHCC>3 in acetonitrile or acetone. When oxidized under such conditions, dialkyl or monoaryl imines give oxaziridines (17). Oxidation of 3,4-dihydroisoquinoline (9) with Oxone initially leads to the formation of oxaziridine (10) which is easily transformed into the corresponding 3,4-dihydroisoquinoline A-oxide (11) upon treatment with catalytic amounts of p-toluenesulfonic acid (Scheme 2.4) (18). 

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. ... 

One can oxidize N-sulfonyl imines to the corresponding oxaziridines using oxidants such as a peracid or oxone [5 b, 93,94], Thus, Davis and coworkers have developed a biphasic procedure for converting imine 278 to frans-oxaziridine 279, in high yield [5b] [Eq. (65)]. Similarly, camphor-derived N-sulfonyl imines 277 and 268 can be oxidized to the endo oxaziridines 280 and 281, respectively [92,93] [Eq. (66), (67)]. Davis and others have now demonstrated the exceptional utility of oxaziridines as oxidants in organic synthesis and, in particular, the value of camphor-derived reagents, such as 280 and 281, in asymmetric synthesis [94,95],... 

The earliest method for synthesizing perfluorinated oxaziridines entailed addition of trifluoromethyl hydroperoxide (287) to a perfluoroimine, followed by elimination of HF mediated by a metal fluoride. The fluoride of choice was the mild reagent KHF2 because it was basic enough to effect the elimination but too weak to ring open the oxaziridine product. Oxidation of imine 288 by this method gave perfluoro-A-methyloxaziridine (289), the first perfluorooxaziridine. In the case of hindered imine 290, no adduct was obtained with hydroperoxide 287, but oxidation to oxaziridine 291 was successful nonetheless with the hydroperoxide in the presence of KF. Presumably the imine was attacked by the hydroperoxide anion, forming the intermediate anion 292. 

The unusual oxaziridine analog 91 has also been synthesized by oxidizing the glycolate imine 90 of diphenyl aminomethylphosphonate 89 with wi-chloroperbenzoic acid (MCPBA). The resulting adduct was thermally quite labile but could be isolated after removing all of the volatile side components in vacuo (2). 

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... 

Oxidation of A-alkyl imines with dimethyldioxirane (DMD) in a solution of dichloromethane-acetone gives nitrones without the apparent formation of oxaziridines (13). Under the conditions of phase transfer, imines can be oxidized into nitrones upon treatment with permanganate ion MnC>4 (19). 

Also, nitrones can be formed by photochemical oxidation (X350 nm) of aldimines in acetonitrile, in the presence of O2 over a TiC>2 suspension (20, 21). Air oxidation of imines into oxaziridines with their subsequent transformation into nitrones, using cobalt catalysts, provides good yields. Utilization of molecular oxygen in the oxidation process seems highly promising due to its cost-effectiveness, availability, and the possibility of industrial application (22). 

Nonequivalence of Oxaziridines from (+)-MPCA Oxidation of Imines ... 

To avoid overoxidation, primary amines (e.g. 128, equation 89) can be converted into Schiff bases with an aromatic aldehyde. Subsequent oxidation of the resultant imines 129 with an excess of peracids produces oxaziridines 130 and/or nitrones 131. Both of them produce hydroxylamines 132 (equation 89) upon hydrolysis in moderate to good overall yields. Yields of hydroxylamines are considerably better if anisaldehyde instead of benzaldehyde is used for the protection . ... 

Imines are oxidized by Oxone to oxaziridines in quantitative yields (equation 62) ... 

The cycloaddition of an oxygen atom to the CN double bond, analogous to the epox-idation of CC double bonds, is rare. For example, when the imine 17 is oxidized with in-situ-generated dioxirane (equation 15), the oxaziridine 18 is obtained as the major... 

Oxaziridines are known thermally to revert to imine N-oxides, and it is not surprising that when heated in presence of isocyanides they undergo the equivalent of a [3 +1] addition (79BAU1648). Although the imino 1,2-oxazetidine was not isolated, its intermediacy was inferred from the isolated decomposition products (Scheme 117). 

Oxidation is generally complete after addition of the oxone solution. The oxidation is monitored by TLC as follows remove approximately 0.5 mL of the toluene solution from the nonstirring solution, spot a 250-micron TLC silica gel plate, elute with methylene chloride and develop with 10% molybdophosphoric acid in ethanol and heating (camphorsulfonyl)imine R = 0.28 and (camphorylsulfonyl)oxaziridine R = 0.62. If (camphorsulfonyl)imine is detected, stirring is continued at room temperature until the reaction is complete (See Note 8). 

The permanganate ion oxidation of imines to nitrones is very much dependent on the reaction conditions. For the investigation of this dependency, reactions with benzylidene-r-butylamine, la, were carried out (equation 8). la was oxidized with m-chloroperbenzoic acid to give the corresponding oxaziridine 3a. As byproduct traces (<3%) of the nitrone 2a, amine 4a and benzaldehyde were formed. The permanganate ion and m-chloroperbenzoic acid may then oxidize the imine in two different ways. 

The oxidation of imines derived from substituted cyclohexanones occurs predominantly from the equatorial direction. However, the product oxaziridines can undergo subsequent equilibration to favor a more stable conformation which places the bulkier nitrogen substituent in an equatorial conformation (equation 44)219. 

The metal-catalyzed oxidation of imines using molecular oxygen as the final oxidant and aldehydes as co-reductants has been studied223. Various transition metal complexes have been tested as catalysts and it is found that cobalt complexes can catalyze the selective oxidation of imines to oxaziridines in good yield (ca 80%) (Scheme 4). 

Diarylnitrone (31) formation from N-substituted, diaromatic imines has been recognized to require the presence of NADPH/O2, and has been proposed to proceed via the intermediacy of an oxaziridine3 possibly arising from reaction of the parent imines with the putative P-450 [FeO]3+ species in analogy to the oxidation of olefins118. Ring cleavage of the oxaziridine then yields nitrone or amide (equation 10). 

Photolytic ring expansion of a spirooxaziridine intermediate was central to the ring expansion of the cyclohexanone 324 to 326 (e.g., R = Bn) after initial imine formation from reaction of 324 with 325 the oxaziridine was then generated by oxidation of the imine with w-chloroperoxybenzoic acid (Scheme 41) <1997JOG654>. 

It should be noted that the related imine-oxaziridine couple E-F finds application in asymmetric sulfoxidation, which is discussed in Section 10.3. Similarly, chiral oxoammonium ions G enable catalytic stereoselective oxidation of alcohols and thus, e.g., kinetic resolution of racemates. Processes of this type are discussed in Section 10.4. Whereas perhydrates, e.g. of fluorinated ketones, have several applications in oxidation catalysis [5], e.g. for the preparation of epoxides from olefins, it seems that no application of chiral perhydrates in asymmetric synthesis has yet been found. Metal-free oxidation catalysis - achiral or chiral - has, nevertheless, become a very potent method in organic synthesis, and the field is developing rapidly [6]. 

In the N-sulfonyl imine-catalyzed sulfoxidation, aqueous hydrogen peroxide serves as the final oxidizing agent, which is clearly of practical advantage. In principle it can be assumed that either an oxaziridine (F, Scheme 10.17) or a hydroper-oxy hemiaminal (H, Scheme 10.17) can result as the active species from the reaction of the N-sulfonyl imine E with hydrogen peroxide (Scheme 10.17). For imine 79 the idea of an intermediate oxaziridine is supported by the experimental finding that oxidation by the isolated oxaziridine and in the catalytic reaction (using 79 and... 

Toda, F., and Ochi, M. (1996) Enantioselective Oxidation of Imines in Inclusion Complexes with a Chiral Host Compound and Preparation of Optically Pure Oxaziridines by Enantiomer Resolution, Enantiomer, 1, 85-88. 

Jorgensen has studied the oxidation of imines 137 to oxaziridines 138 catalyzed by transition metal complexes using molecular oxygen as the stoichiometric oxidant. Optimized... 

Details are now available of the reactions of peracids and of hydrogen peroxide with the imines (10) and (11). The reactions of the product oxaziridines and nitrones with the same two oxidants were also discussed. The reactions of sodium borohydride, benzoyl chloride, and toluene-p-sulphonic acid with the hydroxy-nitrones (12) and (13) have been reported.12 The c.d. spectra of 2-substituted pyrrolidines have been compared with that of conanine (14).13... 

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