Mechanistic insights into the regiodivergent insertion of bicyclo[1.1.0]butanes towards carbocycle-tethered N-heteroarenes

Ring scaffolds constitute important sub-structures in nature and across the chemical industries. However, their straight-forward introduction into a target molecule or cross-linkage between cyclic motifs of choice comprise major challenges for methodology development. Herein, the interconnection of two prominent representatives of the 2D and 3D cyclic chemical space-namely N-heteroarenes and unsaturated carbocycles-in the form of hybrid cyclobutane-tethered N-heteroarenes is targeted. The diastereoselective introduction of decorated cyclobutanes is promoted by the insertion of strained bicyclo[1.1.0]butanes (BCBs) into the C-S bond of C2-thioether aza-arenes. In-depth density functional theory (DFT) studies provide insights on the key factors governing the unexpected regiodivergent insertion outcomes. A broad scope of mono- and bicyclic aza-arenes along with mono- and disubstituted BCBs are shown to be competent. Detailed mechanistic studies support an oxidative activation of the N-heteroarenes.