Organocatalytic Enantioselective Synthesis of Nitrocyclopropanes Bearing a Thioester Group and Three Stereogenic Centers

A two-stage protocol was developed for accessing nitrocyclopropanes that bear a thioester group and three stereogenic centers. This protocol achieves practical overall yields ranging from 54% to 75%, along with high levels of stereoselectivity (single diastereomer with up to 98% ee). Brominated monothiomalonate (Br-MTM) is used as an alpha-bromo thioacetate equivalent, which reacts efficiently with nitroolefins in the presence of a low catalyst loading (0.5 mol%) of cinchona alkaloid squaramide under both "on water" and organic homogeneous conditions. The obtained alpha-bromo-gamma-nitrothioesters undergo an anti-selective decarboxylation and intramolecular S(N)2 cyclization process, leading to the formation of desired cyclopropanes. Control experiments were conducted alongside computational studies in order to gain insights into the observed stereoselectivities.