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

Abstract

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 α‐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 α‐bromo‐γ‐nitrothioesters undergo an anti‐selective decarboxylation and intramolecular SN2 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.