Noncovalent organocatalysis:an open door in the asymmetric nucleophilic epoxidation

"Asymmetric epoxidation holds a venerable place in the organic chemistry since chiral epoxy products are among the most valuable building blocks. Although the Sharpless’s breakthrough paved the way for today’s catalytic epoxide syntheses, only over the last years, have systems been described which allow the asymmetric epoxidation of electron-poor olefins. Asides metal-based catalysis, efficient systems have been devised for the asymmetric organocatalytic epoxidation of enones. Conversely, the application of such strategies to α,β-unsaturated carboxylic acid derivatives is a mostly unexplored field. . Within this context, we pursued our research by exploiting the diphenyl prolinol \/TBHP system to perform a stereoselective organocatalytic epoxidation of α-alkylideneoxindoles, electron-poor olefins bearing two EWG on the opposite sides of the double bond. Particularly, once optimized the oxidative procedure with a pilot substrate (95%Y, 82%ee), we explored the substrate scope by introducing several functional groups on the nitrogen, changing the substituents on the aromatic ring, modifying the EWG and employing novel alkylidene analogs. We always achieved the desired spiroepoxides in excellent yields and quite good enantioselectivity (up to 96%ee), with the contemporaneous challenging formation of two new contiguous quaternary stereocenters Such a successful achievement provides a novel nucleophilic approach to the organocatalytic epoxidation of α,β-unsaturated carboxylic acid derivatives and offers a valuable alternative to the reported electrophilic procedure. Additionally, it demonstrated the action mode of noncovalent catalysis that relies on a H-bond network among substrate, bifunctional catalyst and oxidant as further confirmed by the comparison of the experimental data with deep quantum mechanical calculations.. Finally, these results provide a straightforward access to novel spiro-epoxyoxindole derivatives, extremely attractive intermediates in total synthesis due to the presence of additional moieties capable of further chemical elaboration.. "