Synthesis of Tetraazamacrocycles by Sequential Palladium‐Catalyzed Allylic Substitution Reactions

Abstract

In this study, we focused on the synthesis of tetraazamacrocycles, an essential class of macrocyclic compounds with applications in coordination chemistry, pharmaceuticals, and catalysis. To accomplish this, we developed a ligand‐controlled palladium‐catalyzed allylic substitution approach using bicyclic bridgehead phosphoramidite (briphos) ligands. This approach allowed us to selectively achieve [1+1] and [1+2] allylic aminations between allylic diols and diamines, while avoiding the formation of cyclic [1+1] products. By combining this approach with sequential acetylation and allylic amination, we successfully synthesized tetraazamacrocycles with ring sizes ranging from 16 to 38. These findings demonstrate the potential of a sequential allylation strategy for synthesizing complex molecules with broad applications in the fields of chemistry, pharmaceuticals, and medicine.

Quinoxaline-based azamacrocycles: synthesis, AIE behavior and acidochromism

“…Among the results reported above the reaction with bis(2-aminoethyl)amine (N 3 C 4 ) drew our attention because of the almost quantitative yield (92%) obtained in the runs using PhPF- t Bu ligand. Macrocyclizations driven by transition metal catalyzed (TMC) reaction can give yields above 50, sometimes even 70–75%, 63,76,77 but extremely rarely any higher. Similar or even lower yields are typical for successive formation of macrocycles through reactions which do not need in TMC.…”