Catalytic enantioselective synthesis of alkylidenecyclopropanes

The enantioselective construction of small ring carbocycles provides organic chemists with an enduring challenge.¹ Despite their commercial importance, enantioselective synthetic routes towards alkylidenecyclopropanes (ACPs), a class of small ring carbocycles, remain underdeveloped.^2,3 Importantly, ACPs can be converted into cyclopropanes, a common feature in drug molecules (e.g. Nirmatrelvir, 1),⁴ as well as both naturally occurring and synthetic agrochemicals (e.q. permethrin 2).^5,6 We now describe the facile synthesis of highly enantioenriched alkylidenecyclopropanes through the use of a bifunctional iminophosphorane (BIMP) catalysed, stereo-controlled, strain-relieving deconjugation. Small modifications to the basic catalyst system were used to broaden the scope of the reaction to substrates containing ester, amide, phosphine oxide, and ketone functionalities. Through the design of a suitable substrate and re-tuning of the catalyst’s iminophosphorane moiety, the transformation was effectively applied to the synthesis of a single stereoisomer of the commonplace insecticide permethrin as well as a range of cyclopropane-based insecticide cores. State-of-the-art computational studies were performed to provide detailed insight into the mechanistic pathway and origin of both diastereo- and enantioselectivities.