Multistep Reactions Initiated by Amine‐Based Organometallic Methods

The pursuit of atom‐ and step‐economical pathways to access complex heterocycles and functionalized scaffolds has driven advances in the use of transient and free amine directing groups that exploit native coordination properties for multistep synthesis. Traditional protection‐functionalization‐deprotection sequences, while effective in some circumstances, introduce inefficiencies that compound across multistep syntheses. The following strategies address three critical challenges: 1) eliminating auxiliary installation/removal, 2) enabling multistep functionalization without intermediate isolation (in many cases), and 3) maintaining compatibility with sensitive functional groups. This review aims to collectively summarize the developments in amine‐based synthesis that make use of the amine both as a directing group and a reactive partner in subsequent reaction steps. By analyzing mechanistic insights and substrate scope limitations across these methodologies, one can identify unresolved challenges and provide insight on future directions.