Oxaziridine mediated epoxidation

In the oxaziridine-mediated epoxidations, attack trans to the isopropenyl group is favored for the uncondensed oxaziridine (Table 2, entry 5) the stereochemical analysis is complicated by the fact that the reagent is a racemate and the substrate is enantiomerically pure and, therefore, a total of eight diastereomeric transition states would have to be considered. Utilizing an enantiomerically pure condensed oxaziridine (Table 2, entry 7), high diastereoselectivity can be achieved by double asymmetric induction. 

The spiro transition state is now generally accepted as the mechanism in operation during both dioxirane- and oxaziridine-mediated epoxidation. This conclusion is supported by theoretical and computational studies [31-33]. 

Whereas peracids do not exhibit any face discriminating steric effect in the epoxidation of (S)-limoncne (Table 2, entries 3 and 4), due to the shallow topography of the molecule in the half-chair conformation (in accord with an MM2 simulation168), oxaziridine-mediated and molybdenum-catalyzed epoxidations (Table 2, entries 5 and 7 versus entries 1 and 2) show appreciable, but opposite, diastereoselectivity. 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

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]. 

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]. 

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