The Aminopalladation-Reductive Elimination Process as a Tool for the Solution-Phase Synthesis of 2,3-Disubstituted Azaindole Libraries

摘要

The design of small molecule libraries based on natural products as templates and,hence,the development of procedures that allow for the incorporation of diverse reagents into these molecules are two of the topics of great current interest in combinatorial chemistry.Though azaindoles are relatively scarse as naturally occurring compounds,their bioisosteric relationship with indoles,diffused in a vast number of biologically active natural and unnatural compounds,and their widespread application as pharmaceutical agents make them attractive synthetic targets for the preparation of combinatorial libraries.Traditional methods for the preparation of azaindoles rely on the well-established .Fischer,Madelung,and Reissert procedures,which in general require drastic reaction conditions and afford the desired products in modest yields.Recently,transition metal-catalyzed syntheses of this class of compounds have been described.In particular,azaindoles have been prepared from appropriately substituted pyridines and terminal alkynes through a coupling/cyclization process involving palladium or copper catalysis,an intramolecular Heck reaction of enamine derivatives,and a heteroannulation of internal alkynes according to the procedure developed by Larock for the synthesis of indoles.