Brook Rearrangement as a Carbenoid-Trigger for Ring Expansion of Cyclopropanes to Access Stereo-Defined Highly-Substituted Cyclobutenes

Cyclobutenes represent an important class of structural motifs owing to their presence in many natural products as well as bioactive compounds.Meanwhile, they have also proven to be versatile synthetic intermediates to structurally complex molecules for their high reactivity because of the ring strain.However, efficient methods for the construction of cyclobutenes are still quite limited, especially for stereo-defined highly-substituted ones.In sharp contrast, numerous cyclopropanes’ stereoselective preparations are well established, so the ring expansion of cyclopropanes holds a great promise for the efficient construction of cyclobutenes.In this study, the regio- and diastereoselective copper-catalyzed carbomagnesiation of cyclopropenyl ethers, followed by nucleophilic addition to an acyl silane,Brook rearrangement and ring expansion to give the corresponding cyclobutene as a single isomer in a one-pot operation. Our methodology provides a facile and novel route to access stereo-defined cyclobutenes, particularly poly-substituted ones, bearing a quaternary carbon stereocenter with a high enantiomeric ratio. Additionally, this unique ring expansion paves an attractive way to further understand and make use of classic Brook rearrangement, especially as a feasible carbenoid-trigger.