ABSTRACT
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.
ABSTRACT
Secondary alicyclic amines are converted to their corresponding ring-fused imidazoles in a simple procedure consisting of oxidative imine formation followed by a van Leusen reaction. Amines with an existing α-substituent undergo regioselective ring-fusion at the α'-position. This method was utilized in a synthesis of fadrozole.
ABSTRACT
This Graphical Review provides a concise overview of the manifold and mechanistically diverse methods that enable the functionalization of sp3 C-H bonds in amines and their derivatives.
ABSTRACT
A simple one-pot procedure enables the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the α- and α'-positions of unprotected azacycles. Aryl, alkyl, and alkenyl substituents are introduced via their corresponding organolithium compounds. The scope of this transformation includes pyrrolidines, piperidines, azepanes, and piperazines.