Keywordsepoxidation; peptide; asymmetric catalysis; olefin isostere; fluorine; peptidomimetic The biosynthesis of natural products that contain epoxides represents a powerful stimulus for the study of "epoxidase" enzymes. [i] Likewise, these processes have inspired a generation of science focused on small molecule catalysts that mediate selective epoxidations through a variety of mechanisms. [ii] With respect to the naturally occurring epoxidases, the mechanistic basis of O-atom transfer is often associated with the chemistry of either flavinoid cofactors, P450 enzymes containing a heme group, or chloroperoxidases that lead to stepwise ring formation. [iii] In thinking about the known biosynthetic apparatus for epoxide formation, we became curious about an alternative mode for O-atom transferone based on functional groups available in proteins, but perhaps not well-documented in the biosynthesis of epoxides. In particular, we speculated and recently showed that asparticacid-containing peptides (e.g., 1; Figure 1a) might shuttle between the side-chain carboxylic acid and the corresponding peracid (e.g., 2) creating a catalytic cycle competent for asymmetric epoxidation with turnover of the aspartate-derived catalyst. Such an approach is orthogonal to the Julia-Colonna epoxidation, a complementary peptide-based epoxidation based on a nucleophilic mechanism. [iv] Indeed, as shown in Figure 1b, this new electrophilic epoxidation catalytic cycle mediates the asymmetric epoxidation of substrates like 3 to give products like 4 with up to 92% ee. [v] Mechanistic questions abound in this catalytic system. To date, we have identified a number of relevant aspects. For example, we observed off-catalytic cycle intermediates, including catalytically inactive diacyl peroxides (6). [vi] We also showed that these off-cycle intermediates could be reinserted into the productive pathway through the action of nucleophiles such as DMAP or DMAP-N-oxide (7). On the other hand, the basis of stereochemical information transfer was not immediately clear. Indeed, the high precision delineation of the stereochemical mode of action of chiral catalysts is a critical frontier in the discipline of asymmetric catalysis, whether the catalysts are enzymes or small molecules. With this back-drop, we began a detailed study of the mode of action for catalyst 5.The conversion of 3 to 4 was originally undertaken with the hypothesis that substratecatalyst hydrogen bonding might contribute to transition state organization. [vii] Indeed, a substrate lacking obvious H-bonding capability (phenylcyclohexene) was found to undergo epoxidation with catalyst 5 with low enantioselectivity (~10% ee). Thus, we envisioned several potential loci for contacts between 3 and 5 (Figure 2a). Shown in blue is the site that