Phosphine-Promoted Strain-Release Wittig-Type Functionalization of Bicyclo[1.1.0]butanes via n→σ* Bond Activation

Abstract

Bicyclo[1.1.0]butanes (BCBs) have long served as versatile building blocks in organic synthesis, with their reactivity predominantly governed by radical-mediated or Lewis acid-catalyzed activation of the strained central C–C σ-bond. Herein, we report a metal- and base-free, phosphine-promoted strategy through n→σ* activation, enabling a strain-release Wittig-type olefination with diverse carbonyl compounds. This approach leverages the unique electronic properties of trivalent phosphines to induce ring opening of BCBs, generating zwitterionic phosphonium intermediates that evolve into ylides without requiring an external base, thereby enabling efficient C═C bond formation. The protocol exhibits broad substrate scope, accommodating both aromatic and aliphatic aldehydes and ketones. Mechanistic interrogation, supported by deuterium-labeling experiments and NMR spectroscopy, confirms the intermediacy of a phosphonium ylide and identifies the nucleophilic attack on the BCB σ-bond as the rate-determining step. Furthermore, the synthetic utility of this method is highlighted by gram-scale synthesis and diverse downstream transformations of the alkenylated products.