Aminoalkylation of [1.1.1]Propellane Enables Direct Access to High-Value 3‑Alkylbicyclo[1.1.1]pentan-1-amines

Bicyclo­[1.1.1]­pentanes are effective bioisoteres for aromatic rings, tert-butyl groups, and alkynes. Here we report the first method to synthesize 3-alkylbicyclo[1.1.1]­pentan-1-amines directly from [1.1.1]­propellane via sequential addition of magnesium amides and alkyl electrophiles. The mild reaction conditions tolerate a variety of important functional groups and enable efficient incorporation of several pharmaceutically relevant amines onto the bicyclo[1.1.1]­pentane scaffold. This method’s utility is highlighted by its ability to significantly streamline the syntheses of several important bicyclo[1.1.1]­pentan-1-amine building blocks.