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.