We are pleased to share our latest collaborative work with Professor Fernando Coelho’s group, now published in Organic & Biomolecular Chemistry:
“An asymmetric and theoretical approach to the Morita–Baylis–Hillman reaction using vinyl-1,2,4-oxadiazoles as nucleophiles”
† Thaynan A. B. Chagas, Bruno A. Piscelli, Hugo Santos, Sâmia R. Lima, Rodrigo A. Cormanich,* Fábio S. Fernandes,* and Fernando Coelho*
https://doi.org/10.1039/d5ob00540j
In this study, we report the first enantioselective Morita–Baylis–Hillman (MBH) reaction using a vinyl heterocycle as the nucleophile. Catalyzed by β-isocupreidine (β-ICD), the reaction between vinyl-1,2,4-oxadiazoles and N-substituted isatins delivers highly functionalized products with yields up to 95% and excellent enantiomeric ratios (up to 98:2 er).
Computational studies could elucidate the origin of enantioselectivity and the preference for the R enantiomer. These insights also shed light on the lack of selectivity observed with nitro-substituted isatins.
Importantly, this strategy enabled access to chiral analogues of the natural products phidianidine A and B, offering a promising route for generating novel chiral 1,2,4-oxadiazoles.
Congratulations to the students Thaynan and bruno and all involved in this exciting collaboration!
