Epoxidation with iminium salts

Table 7 Asymmetric epoxidation with iminium salts 71, 74, 76-82 ...

Scheme 12.8 Asymmetric epoxidation with iminium salt 17.

Both chiral ketones and chiral iminium salts have proven their potential as metal-free enantioselective catalysts of epoxidation. The enantiomeric excesses currently observed with chiral ketones are higher than those achieved with iminium salts. In terms of practicability, the Shi ketone 10, an inexpensive and readily available... 

Epoxidation conditions Iminium salt (5 mol%), Oxone (2 equiv), Na2CO3 (4 equiv), MeCN H2O (1 1), 0 "C, 2 h. Enantiomeric excess determined by NMR with Eu(hfc)3 (0.1 mol equiv) as chiral shift reagent or by Chiral HPLC on a Chiracel OD column. 

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). 

While most of the iminium salts studied are cyclic, several acyclic iminium salts have also been investigated. In 1997, Armstrong and coworkers reported the use of acyclic iminium salt 83 as chiral epoxidation promoter (Fig. 27) [156, 157]. 1-Phenylcyclohexene oxide could be obtained in 100% conversion and 22% ee with stoichiometric amounts of 83. In 2002 acyclic iminium salt 84, prepared from L-prolinol, was investigated by Komatsu and coworkers, and cinnamyl alcohol was epoxidized in 70% yield and 39% ee (Fig. 27) [158]. 

In 2001, Yang and coworkers studied the use of in situ generated acyclic iminium salts as epoxidation catalysts [159]. Epoxidations of a number of aUcenes proceed with 20-50 mol% of amine 85 and aldehyde 86 with Oxone as the primary oxidant (Fig. 28.) Methylstilbene can be obtained in 100% conversion and 59% ee. 

The epoxidation of olefins catalyzed by iminium salts and amines (or ammonium salts) is emerging as a new technique for the functionalization of simple aUcenes. These catalysts have relatively simple structures and hence are easily produced at scale they offer potential as green oxidation catalysts. These organic salts are effective oxygen transfer reagents towards electron-rich unfunctionalized olefins. For the iminium salt systems oxone oxidizes an iminium salt to the oxaziridi-nium intermediate, which then transfers oxygen to the olefin and as oxone reacts readily with iminium ions to regenerate the oxaziridinium species catalyti-cally, efficient oxidation is possible. 

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. 

Homologous biphenyl and binaphthyl tertiary azepines (4) and quaternary iminium salts, prepared from (+)-(5,5 )-L-acetonamine, behave as effective catalysts for the enantioselective epoxidation of unfunctionalized alkenes with Oxone (ee up to 83%).113... 

Iminium salt-catalysed epoxidation reactions have been carried out in organic solvents, including dichloromethane and acetonitrile, with tetraphenylphosphonium... 

Pentacarbonyl[methyl(methoxy)carbene]tungsten and other carbene complexes containing a hydrogen atom a to the carbene carbon atom react with butyllithium (but also with OMe" ) at low T to generate carbene anions. The moderate reactivity of these carbene anions toward carbon nucleophiles, including epoxides, aldehydes, a-bromoesters and a, -unsaturated carbonyl compounds can be used to prepare carbene complexes inaccessible via other synthetic routes (see refs. 7-9). The anion generated by treatment of (CO)5Cr[C(OMe)Me] with BuLi in THF at — 78°C is isolated as the air-stable bis(triphenylphosphane)iminium salt . 

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. 

Armstrong a al. found that stoichiometric use of chiral pyrrolidine-derived iminium salt 63 (Figure 13 could only be isolated in impure form) in the asymmetric epoxidation of phenylcyclohexene gave the oxirane with 22% ee < 1999T2341 >. 

A variation of the Sharpless asymmetric epoxidation is to employ chiral hydroperoxides. The chiral iminium salt 89 has moderate enantiocontrol for epoxidation. Quatemized cinchona alkaloids can serve as chiral catalyst and phase-transfer agents in epoxidation of enones with NaOCl. Enones are also epoxidized by oxygen in the presence of diethylzinc and A-methylpseudoephedrine, whereas IZj-enones are submitted to enantioselective epoxidation by t-BuOOH-O-PrO),Yb and the BINOL 90. 

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). 

Recently, two other groups have shown that exocyclic iminium salts can be useful mediators in asymmetric epoxidation. Komatsu has developed a system based on ketiminium salts [14], prepared through the condensation of aliphatic cyclic amines with ketones. A chiral variant was also produced, derived from prolinol and cyclohexanone, which gave 70% yield and 39% ee for cinnamyl alcohol (Scheme 5.7). 

More recently Bohe, a former co-worker with Lusinchi, has reported an improved achiral catalyst that prevents some of the common side reactions observed in iminium salt-mediated epoxidation [18]. Two factors are known to reduce the catalytic efficiency of the epoxidation process hydrolysis of the iminium salt directly by the reaction medium, which generally only affects the acyclic systems and loss of active oxygen from the intermediate oxaziridinium species, through a reaction that does not regenerate the iminium species, which... 

This iminium salt was tested in the catalytic asymmetric epoxidation of several alkenes at 0 °C, and a comparison of the results with those obtained using catalyst (17) is presented in Table 5.2 [24]. These results indicated that catalyst (24) in general induces much higher enantioselectivity in asymmetric epoxidation than others that were screened, providing in some cases dramatic improvements in ee over catalyst (17). 

Epoxidation reactions were carried out using these new iminium salts, and a comparison of the results obtained with the original dihydroisoquinolinium catalysts (17) and (24) is displayed in Table 5.3. It is clear that both of the new... 

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