Oxidative sulfonylarylation of strained C–C σ-bonds for the synthesis of 3-spirocyclic oxindoles initiated by insertion of sulfur dioxide

Abstract

The development of difunctionalisation reactions of C–C σ-bonds remains a long-standing challenge, but is very significant in synthetic chemistry, considering that C–C σ-bonds are ubiquitous in organic molecules. However, there are limited methods for cleaving C–C σ-bonds because C–C σ-bonds are typically inert. Taking advantage of ring strain to activate C–C σ-bonds in polycyclic carbocycles is an effective method. Here an oxidative sulfonylarylation of the central C–C σ-bond of bicyclo[1.1.0]butanes and bicyclo[2.1.0]pentanes driven by ring strain release is described. This protocol uses Na₂S₂O₅ as a sulfur dioxide surrogate along with 4-alkyl 1,4-dihydropyridines as radical precursors for accessing sulfonyl radicals, and follows a sequential C–C/C(sp²)–H functionalisation to provide rapid access to a diverse library of 3-spirocyclic oxindoles bearing a sulfonylated cyclobutyl moiety with good functional group compatibility. In addition, the synthetic utility of this method is further illustrated by the facile synthetic transformations of drug-derived molecules.