Enantioselective Access to Alkylidenecyclopropanes via Base-Catalyzed 1,3-Hydrogen Shift

Keywords

alkylidenecyclopropanes - BIMP - superbase - strain release

Significance

Dixon and co-workers present an enantio- and diastereoselective (up to 99.5:0.5 er; > 20:1 dr) synthesis of alkylidenecyclopropanes in high yields (74–98 %) through a strain-relieving, deconjucative, prototropic shift. Key to this discovery has been the use of fine-tuned bifunctional iminophosphorane (BIMP) catalysts, in a Goldilocks zone between sufficient basicity for productive reactivity, yet not so high as to induce epimerization of the newly formed stereocenter.

Comment

The presented method allows the synthesis of cyclopropane motifs, which are featured in a variety of drug molecules and agrochemicals. Importantly, the Dixon group demonstrates how the single stereoisomer (1R,3R)-cis-permethrin can be accessed using their method. Permethrin is a member of the WHO’s Essential Medicines List. DFT studies confirm the importance of the appended amide in the catalyst structure, as it is crucial for H-bond activation of the thiourea and catalyst activity.

Publication History

Article published online:
30 October 2025