Synthesis of Bicyclo1.1.1pentane Bioisosteres of Internal Alkynes and para‐Disubstituted Benzenes from 1.1.1Propellane

We report a general preparation of arylated bicyclo1.1.1pentanes through the opening of 1.1.1propellane with various arylmagnesium halides. After transmetalation with ZnCl2 and Negishi cross-coupling with aryl and heteroaryl halides, bis-arylated bicyclo1.1.1pentanes are obtained. These bis-arylated bicyclo1.1.1pentanes may be considered as bioisosteres of internal alkynes. Bioisosteres of tazarotene and the metabotropic glutamate receptor 5 (mGluR5) antagonist 2-methyl-6-(phenylethynyl)pyridine were prepared and their physicochemical properties were evaluated.