Recent Advances in CH Bond Functionalization Using Traceless N-Functionalized Directing Groups

Abstract

The chelation-assisted CH bond activation with proper directing groups not only promotes the reaction efficiency but also enables selective CC or CX bond formation at the specific positions. Among them, the traceless directing groups (TDGs) strategy is highly attractive since it allows the in situ removal of directing groups after the directed CH bond functionalization. On the other hand, N-containing substrates, e.g., N-heterocycles, amines, and oximes, are of great importance in both organic synthesis and drug discovery. The directed site-selective CH bond functionalization of nitrogen-based substrates using TDG strategy constitutes an ideal solution to access more elaborate molecules. In this context, this review focus on the development of diverse traceless N-functionalized directing groups and their application in the CH bond functionalization, along with mechanistic insights into the directing group removal steps. Typical examples that use N-functionalized TDGs, such as N-oxides, nitrones, N-nitroso groups, hydrazyl groups, N-acyl groups, and other nitrogen-functionalized groups, have been documented in this review, aiming to give a timely comprehensive overview and stimulate the development of more efficient methodologies.