1- Phenylcyclohexene oxides

In 1996, Aggarwal and coworkers synthesized binaphthyl-based iminium salt 76 via oxidation and methylation from binaphthylamine (Scheme 15) [147], Catalyst loading of 5 mol% is sufficient to catalyze the epoxidation of a number of olefins in good yield. Up to 71% ee can be obtained for 1-phenylcyclohexene oxide using this catalytic system (Table 7, entry 8). 

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]. 

Armstrong has developed a-fluoro-W-ethoxycarbonyltropinone 54 as an asymmetric catalyst for the enantio-selective epoxidation reaction 1-phenylcyclohexene oxide is produced in 97% yield and 69% ee (Scheme 20) <1998CC621>. Analogously, the use of a-acetoxy-8-oxabicyclo[3.2.1]octan-3-one 55 results in 71% yield and 98% ee (Scheme 20) <2001TA2779>. Tropinone catalyst 54 gives only low levels of enantioselectivity in the asymmetric epoxidation of dihydronaphthalene and an enol benzoate (Scheme 20) <2002JOC8610>. 

Mechanisms of acid-catalyzed hydrolysis of 1-phenylcyclohexene oxides, indene oxides and 1,2,3,4-tetrahydronaphthalene-l,2-epoxides 264... 

With the catalysts in hand, we were able to test their effectiveness in several epoxidation reactions. Initially, we screened the catalysts with our usual test substrates, 1-phenylcyclohexene, a-methylstilbene and triphenylethylene (Table 5.5). Catalyst 33a showed the best reaction profile, being by far the most reactive. For example, in the presence of 33a, 1-phenylcyclohexene oxide was produced in 69% yield with 91% ee in imder 20 min, while the other catalysts (apart from ent-33a) were less selective, and the reactions were slower. The isopinocamphenyl moiety offers little enantiocontrol, leading to epoxides with only moderate ees. The poor reactivity of catalysts 33b-d is highlighted by the attempted epoxidations of a-methyl stilbene and triphenyl ethylene, where no epoxides were formed after 4 h. 

Temperature studies Several reactions with our test substrate 1-phenylcyclohexene were performed using catalyst (31) and our dihydroisoquinolinium catalyst (24) under these new conditions. Runs were conducted using 10 mol% of catalyst over a range of temperatures the results obtained are displayed in Table 5.9. It is important to note here that the corresponding catalysts derived from the (—)-IPC amine (17 and 31) gave poor conversions and ees under these conditions. For example, catalyst (31) (10 mol%) afforded only 60% conversion to 1-phenylcyclohexene oxide and 13% ee after 2 h at —40 °C. As a comparison, the reported aqueous/acetonitrile results are included [24,34],... 

An appreciable range of cis-trans product ratios has been found in ring-opening reactions of meta- and pora-substituted 1-phenylcyclohexene oxides. Suspensions of a series of these compounds (276) in 0.02 mol 1 H2SO4 at 25 °C for 24 h gave products (277) and (278) together with 3 % of minor products, which were shown not to be... 

Rate and product studies have been carried out for the hydronium ion-catalysed hydrolysis of 1-phenylcyclohexene oxide and its p-OMe and p-Me derivatives in 1 9 dioxane-water solution. The cis. trans diol ratio for hydrolysis of this series of epoxides does not systematically increase with increase in the electron-donating ability of the para-substituent, contrary to conclusions in the literature. The detailed results of these studies are in accord with a mechanism involving rate-limiting formation of a carbocation intermediate, followed by partitioning of this intermediate to diol products, with the pathway leading to the more stable m-diol being energetically favored. ... 

After establishing oxo ammonium salts (Fig. 1.3) as useful mediators in the catalytic epoxidation of several alkenes [25, 26], Demnark developed two chiral systems which imparted moderate enantioselectivities (Fig. 1.3), catalyst 6, for example, prodncing 1-phenylcyclohexene oxide with 58% ee. 

Shi has also recently reported asymmetric epoxidation mediated by alkahne hydrogen peroxide [44,45]. High yields and ees were obtained under these reaction conditions with up to 95% ee for 1-phenylcyclohexene oxide using the original fructose derived catalyst 10. Peroxyimidic acid 11 is postulated to be the active oxidant (Scheme 1.15). 

Davis has described many examples of asymmetric epoxidation mediated by oxaziridines. The first chiral oxaziildine reported was derived from bromocamphor 17, but the observed enautioselectivities were low, the best being 40% ee for 1-phenylcyclohexene oxide (Scheme 1.21) [54]. 

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