Oxaziridinium salts

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

Isolated or in situ generated oxaziridinium salt 67 efficiently epoxidizes various olefins in good yields [133-135],... 

In 1993, Bohe and coworkers synthesized enantiomerically pure oxaziridinium salt 71 by methylation with Meerwein s salt and oxidation with mCPBA from dihydr-oisoquinoline 68 (Scheme 13) [136,137], Alternatively, 71 could also be produced by switching the reaction order. Epoxidations were carried out with either... 

Recently, oxaziridinium salts derived in situ from chiral iminium salts (1 and 2) and Oxone were found to catalyze epoxidation with moderate-to-good enantioselectivity (up to 73% ee) (Scheme 6B.4) [6], Although the substrates are limited to conjugated olefins, this reaction has an advantage in being catalytic with respect to chiral iminium salts. 

The reaction mechanism for A-oxidation by performic acid has been studied by AMI calculation methods.174 The iminium salt A-mcthyl-3,4-dihydroisoquinolinium p-toluenesulfonate has been used to catalyse the oxidation of the azo dye calmagite by peracetic acid. The mechanism at pH 10 involves peracid oxidation of the quinolinium ion to form an oxaziridinium salt, which then acts as an oxygen transfer agent for oxidation of cahnagite.175 The presence of lithium salts affects the course of the reaction determining the formation of benzoyl peroxide and benzoic acid as final products in the oxidation of benzaldehyde by perbenzoic acid.176,177... 

As shown in cycle (b) in Scheme 10.1, the iminium-oxaziridinium pair can also effect catalytic asymmetric epoxidation of alkenes. Early work in this field by Bohe et al. included investigation of the norephedrine-derived oxaziridinium salt 34 (33% ee in the catalytic epoxidation of traws-stilbene [41] ee up to 61% was achieved when 34 was employed stoichiometrically [42]), or the L-proline-derived material 35 (39% ee in the epoxidation of trans-3-phenyl-2-propenol [43]). Rapid... 

Closely related to the ketone/Oxone epoxidation system is the use of iminium salts as promoters. As isolated oxaziridinium salts are known to effect alkene epoxidation [38], these are presumed to be the reactive intermediates in this catalytic system (see Scheme 12.1 X = NR.2+). The first asymmetric example used the dihydroisoquinolinium-based system 15 (Fig. 12.7), which afforded 33% ee for the epoxidation of F-stilbene [39]. 

Calculations [46] and studies of intramolecular oxaziridinium epoxidations [47] suggest that, like their dioxirane counterparts, these epoxidation processes proceed via spiro-transition states. However, the iminium epoxidations are generally more substrate-specific than those using dioxiranes, and models to explain the observed trends in stereocontrol have proved more difficult to construct. One complication is the possibility of formation of diastereomeric oxaziridinium salts from most of the iminium catalysts. Houk has rationalized computationally the observed enantioselectivity with Aggarwal s catalyst 16 [46]. The results of a recent study by Breslow suggest that hydrophobic interactions are important in these processes [48], and aromatic-aromatic interactions between catalyst and substrate may also play a role. 

A particularly complicated reaction is reported to occur43,47 with a steroidal enamine. Formation of the products can be explained in terms of the intermediacy of an oxaziridinium salt. 

The first use of an enantiomerically pure oxaziridinium salt to catalyze asymmetric epoxidation (trans stilbene oxide produced with 33% ee using 61 (Figure 13)) was reported by Lusinchi and co-workers in 1993 <1993TL7271> Subsequently, it was reported that phenylcyclohexene is converted to the corresponding epoxide with just 5% ee using stoichiometric quantities of 61 <1999T141>. 

This remains a developing area for the synthesis of chiral oxiranes and has attracted interest from several research groups. As with the use of dioxiranes (above), it is not necessary to form the reactive oxaziridinium salt rather, the epoxidation reaction can be mediated by the corresponding iminium salt and Oxone. 

Brief reports have been made about two unusual oxaziridine derivatives. A quaternary oxaziridinium salt apparently reacts with nucleophiles at oxygen in any case, this salt suffered deoxygenation by some process. Finally, the per-fluorinated oxaziridine 59, undergoes attack exclusively at nitrogen to produce amide derivatives ... 

Bohe, L., Lusinchi, M., Lusinchi, X. Oxygen atom transfer from a chiral oxaziridinium salt. Asymmetric epoxidation of unfunctionalized olefins. Tetrahedron 1999, 55,141-154. 

The formation and the oxidative properties of an oxaziridinium salt have been reported. With methyl fluorosulphonate the oxaziridine (30) led to the oxaziridinium salt (36) which was stable as a crystalline product at room temperature, but unstable in solution, giving (37), also obtained from (38) with methyl fluorosulphonate. NaBHt reduction of (36) led to (35). Peroxidic reactivity of (36) was shown by oxygen transfer from (36) to the imine (38) with formation of the nitrone (39) (Scheme 5). 

Enantiomerically pure oxaziridinium salt (187) was prepared as shown in Scheme (34) <93TL727i>. Oxidation of (185) with MCPBA in MeOH gave a 9 1 mixture of oxaziridine diastereoisomers of which (186) was the major one as determined by x-ray diffraction. 

In the book, the section on homogeneous catalysis covers soft Pt(II) Lewis acid catalysts, methyltrioxorhenium, polyoxometallates, oxaziridinium salts, and N-hydroxyphthalimide. The section on heterogeneous catalysis describes supported silver and gold catalysts, as well as heterogenized Ti catalysts, and polymer-supported metal complexes. The section on phase-transfer catalysis describes several new approaches to the utilization of polyoxometallates. The section on biomimetic catalysis covers nonheme Fe catalysts and a theoretical description of the mechanism on porphyrins. 

In the case of iminium salts [38,204], the group of Page has shown that the intermediate is an oxaziridinium salt generated by a single oxygen atom transfer from a TPPP as determined by H NMR [510] (see Chapter 5). Calculations of the transition state indicate that the transition state is synchronous [511]. 

TiO2/SiO2, Ag-Cu alloys, soft Pt(II) Lewis acids, MTO, oxaziridinium salts, NHPI, polyoxometallates, phase-transfer systems, polymer-supported complexes, calixarene complexes, and biologically based systems. 

M. R. Biscoe, R. Breslow, Oxaziridinium salts as hydrophobic epoxidation reagents Remarkable hvdrophobically-directed selectivity in olefin epoxidation, ]. Am. Chem. Soc. 127 (2005) 10812. 

Oxaziridinium Salt-Mediated Catalytic Asymmetric Epoxidation Philip C. Bulman Page and Benjamin R. Buckley ... 

Oxaziridinium salts are the quartemized analogues of oxaziridines, and as a result of being more electrophilic, transfer oxygen more efficiently to nucleophilic substrates. The first oxaziridinium salt, described by Lusinchi in 1976 [1-3], was based on a steroidal pyrrolinic skeleton. Through peracid oxidation of the steroidal imine and quatemization using methylfluorosulphonate, it was shown that an oxaziridinium species could be formed (Scheme 5.1). This new species was rather unstable, and upon decomposition reverted to an iminium salt, which could be directly prepared from the imine. However, it was not until some 11 years later that the potential of this type of system to transfer oxygen was realized [4,5]. 

Using an oxaziridinium salt derived from dihydroisoquinoline, Lusinchi was able to transfer the oxygen atom to several simple alkenes in good yield (Scheme 5.2) [5,6]. Following this work, the first enantiomerically pure oxaziridinium salt was prepared [7]. Quaternization of chiral oxaziridine (1), derived from (lS,2R)-(+)-norephedrine, produced the oxaziridinium salt (2) (Scheme 5.3). 

SCHEME 5.1 The first example of an oxaziridinium salt developed by Lusinchi. 

SCHEME 5.2 Oxygen transfer to alkenes mediated by a oxaziridinium salt derived from tetrahydroisoquinoline. 

Oxaziridinium Salt-Mediated Catalytic Asymmetric Epoxidation 179... 

SCHEME 53 The first enantiomerically pure oxaziridinium salt derived from (lS,2R)-(+)-norephidrine. 

SCHEME 5.4 Catalytic cycle for epoxidations mediated by oxaziridinium salts. 

This oxaziridinium salt was also able to transfer oxygen to olefins, and induced moderate enantiocontrol, epoxidizing frans-stilbene with 33% ee. With the side product of the reaction being an iminium salt, there was potential to develop this chemistry catalytically. If this iminium salt could be re-oxidized to the oxaziridinium in situ, catalytic transfer of oxygen to alkenes could be achieved (Scheme 5.4). 

Lusinchi s group has reported the only X-ray determination of an oxaziridinium salt, of compoimd 2 [7,10]. Its geometry is similar to that of the parent oxaziridine, and the N-O bond length of 1.468 A in the oxaziridinium salt is shortened compared with the mean bond length of 1.508 A observed for oxaziridines. It is also interesting to note that the oxaziridine ring is perpendicular to the isoquinoline ring. 

Armstrong has also reported an in situ epoxidation, mediated by an intramolecular oxaziridinium salt, which gave good regioselectivity (Scheme 5.9) [16]. 

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