Alicyclic-Amine-Derived Imine-BF₃ Complexes: Easy-to-Make Building Blocks for the Synthesis of Valuable α-Functionalized Azacycles

A new strategy to access α-functionalized alicyclic amines via their corresponding imine-BF₃ complexes is reported. Isolable imine-BF₃ complexes, readily prepared via dehydrohalogenation of N-bromoamines in a base-promoted/18-crown-6 catalyzed process followed by addition of boron trifluoride etherate, undergo reactions with a wide range of organometallic nucleophiles to afford α-functionalized azacycles. Organozinc and organomagnesium nucleophiles add at ambient temperatures, obviating the need for cryogenic conditions. In situ preparation of imine-BF₃ complexes provides access to α-functionalized morpholines and piperazines directly from their parent amines in a single operation. α-Functionalized morpholines can be elaborated further, for instance by installing a second substituent in the α'-position.