Epoxidation trans-disubstituted olefins

During the early development of the Jacobsen-Katsuki epoxidation reaetion, it was elear that trans-disubstituted olefins were very poor substrates (slow reaetion rates, low enantioseleetivity) eompared to cis-disubstituted olefins. The side-on approaeh model originally proposed by Groves for porphyrin epoxidation systems was used to rationalize the differenees observed in the epoxidation of the cis and trans-disubstituted elasses (Seheme 1.4.7). ... 

Scheme 3.28 Epoxidation of trans-disubstituted olefins with ketone 39 [35]...

Two successful strategies for the enantioselective synthesis of trans-epoxides by means of oxo-metal catalysis have been discovered. The stereospecific epoxidation of frans-olefins offers a direct route to trans-epoxides, although progress in this area has been limited (see Sect. 2.2.1). Alternatively, the [Mn(salen)]-catalyzed epoxidation of cis-disubstituted olefins in the presence of alkaloid-derived phase-transfer catalysts such as 24 resulted in the formation of the transepoxide as the major, and in some cases nearly exclusive, product (Scheme 6)... 

This catalytic system provides high enantioselectivities for a range of epoxides (Figure 19.2), including those derived from trisubstituted and traus-1,2-disubstituted alkenes, with complete stereospecificity (retention of the alkene geometry in the epoxide product) [17]. The reaction has been shown to be chem-oselective for the alkene of enynes [18], provided monoepoxides upon reaction with conjugated trans-dienes [19] and afforded up to 93% ee for the asymmetric epoxidation of fluoro-olefins [20]. However, decreased enantioselectivity was observed for both cis- and terminal alkenes. The catalytic system has also been applied to the resolution and desymmetrization of cyclic trisubstituted alkenes [21]. 

SCHEME 35.16. Enantioselective epoxidation of trans-disubstituted and trisubstituted olefins with fructose-derived ketone 62 as a highly reactive and enantioselective catalyst. 

Optically active epoxides are found in many natural products [213] and are highly versatile intermediates and building blocks. Asymmetric epoxidations of double bonds have long been employed using metal-mediated methods such as the Sharpless [214] and Jacobsen-Katsuki [215, 216] epoxidation. Metal-free asymmetric epoxidations are mostly mediated by chiral dioxiranes and oxaziridines. Dioxiranes or their respective precursor ketones represent some of the oldest and most versatile organocatalysts for the asymmetric epoxidation of olefins. They are particularly useful for unfunctionalized trans-, disubstituted, trisubstituted and terminal olefins [217-224]. 

In 1997 Shi used a series of pseudo-C -symmetric ketones 404 bearing two fused rings at each side of the carbonyl group [281, 282]. Ketones 404 are characterized by good enantioselectivities (96% ee in the epoxidation of phenylstilbene), even for the epoxidation of electron deficient olefins. Overall, ketones 404 are less enanti-oselective than 376 for the epoxidation of trans-, disubstituted, and trisubstituted olefins. Also, the sterically relaxed ketones 405 and 406 with a CHj-group next to the keto-group show lower enantioselectivities and reactivities for the epoxidation. Zhao et al. reported 85% ee for stilbene with catalyst 406 (Fig. 7.20) [283]. 

A catalytic amount of ketone 26 was used to investigate the substrate scope of the asymmetric epoxidation. High enantioselectivities can be obtained for a wide variety of trans- and trisubstituted olefins (Table 3, entries 1 ) [54]. Simple trans-olefins, such as franx-7-tetradecene, can be epoxidized in high yield and enantiomeric excess, indicating that this asymmetric epoxidation is generally suitable for frani-olefms. 2,2-Disubstituted vinyl silanes are epoxidized in high ees (Table 3, entries 5, 6) and enantiomerically enriched 1,1-disubstituted epoxides can be... 

The substrate scope of this epoxidation was subsequently investigated using a variety of olefins with a catalytic amount of ketone 1 (usually 20-30 mol%). A variety of hms-substituted and trisubstituted olefins have been shown to be effective substrates (Table 10.1),39 and the high ee obtained with hms-7-tetradecene suggests that this epoxidation is quite general for simple trans-olefins (Table 10.1, Entry 5). Various functional groups such as ethers, ketals, esters, and so on are compatible with the epoxidation conditions (Table 10.1). A variety of 2,2-disubstituted vinylsilanes... 

Compared with chiral manganese porphyrin complexes [50], the use of the Mn-salen catalysts results generally in ee s higher than 90% and yields exceeding 80% [39, 58]. A wide range of oxidants including hypochlorite [58], iodosylbenzene [58], or m-chloroperbenzoic acid (m-CPBA) can be applied [59]. Excellent ee s are observed for epoxidation reactions of cix-disubstituted alkenes and trisubstituted alkenes catalyzed by the Mn-salen complexes 11 and 12, employing iodosylbenzene as the oxidant. In sharp contrast, the epoxidation of trans-olefins showed moderate selectiv-... 

---