Dioxirane-mediated enantioselective epoxidations

The ability of non-C2 symmetric ketones to promote a highly enantioselective dioxirane-mediated epoxidation was first effectively demonstrated by Shi in 1996 [114]. The fructose-derived ketone 44 was discovered to be particularly effective for the epoxidation of frans-olefins (Scheme 17 ). frans-Stilbene, for instance, was epoxidized in 95% ee using stoichiometric amounts of ketone 44, and even more impressive was the epoxidation of dialkyl-substituted substrates. This method was rendered catalytic (30 mol %) upon the discovery of a dramatic pH effect, whereby higher pH led to improved substrate conversion [115]. Higher pH was proposed to suppress decomposition pathways for ketone 44 while simultaneously increasing the nucleophilicity of Oxone. Shi s ketone system has recently been applied to the AE of enol esters and silyl enol ethers to provide access to enantio-enriched enol ester epoxides and a-hydroxy ketones [116]. Another recent improvement of Shi s fructose-derived epoxidation reaction is the development of inexpensive synthetic routes to access both enantiomers of this very promising ketone catalyst [117]. 

Fluorine-containing ketones have proven to be one of the most successful types of catalyst for dioxirane-mediated epoxidation [27]. Demnark has shown that good to excellent enantioselectivities can be achieved with catalyst 9 for tra 5-olefins (Scheme 1.10). However, catalyst loadings are high (30 mol%) [28]. 

A breakthrough in dioxirane-mediated epoxidation was achieved by Shi in the late 1990s. He reported excellent ees for a wide variety of snbstrates nsing the frnctose-derived ketone 10 [32], This catalyst is easily prepared in two steps, and typical enantioselectivities range from 80% to 95% ee. However, the chiral ketone decomposes under the reaction conditions (pH 7-8), presnmably throngh Baeyer-VUliger oxidation, and initially a large excess of the mediator had to be nsed (3 equivalents, with respect to the snbstrate) (Scheme 1.12). 

In 1996 Yang first reported the asymmetric epoxidation of olefins mediated by a symmetric dioxirane generated from the corresponding ketone [22]. The chiral ketone was derived from BINAP, and exhibited enantioselectivities typically between 5% and 50% ee under stoichiometric conditions, and 87% ee in the epoxidation of trans-4,4 - diphenylstilbene. With modification of the original C2 symmetric ketone and development of the reaction to run catalytically, Yang was able to increase the enantioselectivity of the process [23, 24], With very hindered alkenes, such as frans-4,4 -diterf-butylstilbene, enantioselectivities of up to 95% ee were achieved (Scheme 1.9). 

Several other attempts at producing highly enantioselective dioxirane-based catalysts for asymmetric epoxidation have been reported [29, 30] of these Armstrong s tropinone-derived a-fiuoroketone was found to be a good mediator (Scheme 1.11)... 

Shi s Highly Enantioselective Dioxirane Epoxidation Mediated by a Fructose-derived Dioxirane... 

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