Synthesis of Saturated Five-Membered Nitrogen Heterocycles via Pd-Catalyzed C N Bond-Forming Reactions

Saturated five-membered nitrogen heterocycles, such as pyrrolidines, indolines, and isoxazolidines, appear as subunits in a broad array of biologically active and medicinally significant molecules [1]. As such, the synthesis of these compounds has been of longstanding interest. Many classical approaches to the construction of these heterocycles involve the use of C N bond-forming reactions such as reductive amination, nucleophilic substitution, or dipolar cycloaddition for ring closure [2]. Although these methods have proven quite useful, their substrate scope and functional group tolerance is often limited. In recent years, a number of powerful new transformations have been developed that involve the use of palladium-catalyzed C N bond-forming reactions for construction of the heterocyclic ring [3]. These transformations frequently occur under mild conditions, tolerate a broad array of functional groups, and proceed with high stereoselectivity. In addition, the use of palladium catalysis allows for highly convergent multicomponent coupling strategies, which generate several bonds and/or stereocenters in a single process. This chapter describes recent approaches to the synthesis of saturated five-membered nitrogen heterocycles via Pd-catalyzed C N bond forming reactions.