Unlocking iminodioxocines and amine-bis(phenols) via sterically guided ammonia condensation: a shortcut to tunable ONO pincer ligands

Abstract

A sterically controlled pathway towards iminodioxocines, hydrobenzamides and ONO pincer ligands – amine-bis(phenols) – is developed by exploiting the reaction between sterically hindered salicylaldehydes and ammonia. Iminodioxocines, which are unlocked by this (first) general pathway, show unprecedented reactivity towards common organolithium reagents, enabling the diastereoselective synthesis of amine-bis(phenols) in almost quantitative yields. The corresponding 2-step procedure – to replace the previous low-yielding 5-step synthetic protocol – addresses the key challenges of the traditional Mannich condensation, such as the failure to introduce NH functionalities into the amine-bis(phenol) core and substituents into its benzylic positions. With the t-butyl and isopropyl groups boosting the steric bulk and the benzylic functionalization inducing the chirality, these ONO pincer ligands are highly promising candidates for asymmetric metal-catalyzed reactions, including hydroamination, epoxidation and olefin polymerization. By enabling multigram-scale synthesis of amine-bis(phenols) from simple starting materials, such as ammonia and salicylaldehydes, the developed methodology offers a versatile platform for designing next-generation catalysts with broad industrial applications in polymer and fine chemical synthesis.