A Diazo-free Equivalent of the Unsubstituted Carbyne Cation: Straightforward Synthesis of Naphthalenes and Pyridines via [ 12/13 CH] + Insertion

High Resolution Image Download MS PowerPoint Slide Stable isotope labeling is a crucial technique in pharmaceutical research to understand the mode of action and metabolism of new drug candidates; however, its utility is often jeopardized by the synthetic challenges associated with the installation of the isotopic label into the core of the structures under study. Herein, we address this problem for the case of 13 C-labeled naphthalene and pyridine building blocks. Our synthetic protocol utilizes the sulfonium sulfaneylidene salt 1, a benchtop stable reagent that does not incorporate diazo functionalities in its structure; yet, under Rh-catalysis, it efficiently acts as a synthetic equivalent of the simplest conceivable carbynyl cation, the [CH] + fragment. Mechanistic experiments supported by DFT calculations suggest the initial formation of a sulfonio-substituted Rh(II)-carbene that reacts with indenes or pyrroles to initially form sulfonio-substituted cyclopropanes; the diastereoselectivity of this step being inconsequential because both isomers interconvert under the reaction conditions. Subsequent electrocyclic ring expansion with the concomitant elimination of dibenzothiophene delivers the desired naphthalenes or pyridines.