Combining Imine Condensation Chemistry with [3,3] Diaza-Cope Rearrangement for One-Step Formation of Hydrolytically Stable Chiral Architectures

Dynamic covalent chemistry (DCC) has, in recent years, provided valuable tools to synthesize molecular architectures of increasing complexity. We have also taken advantage of imine DCC chemistry to prepare TPMA-based supramolecular cages for molecular recognition applications. However, the versatility of this approach has as a major drawback the intrinsic hydrolytic lability of imines, which hampers some applications. We present herein a synthetic strategy that combines the advantages of a thermodynamic-driven formation of a supramolecular structure using imine chemistry, together with the possibility to synthetize chiral hydrolytically stable structures through a [3,3]-sigmatropic rearrangement. A preliminary mechanistic analysis of this one-pot synthesis and the scope of the reaction are also discussed.

Automated summary

Dynamic covalent chemistry (DCC) has been valuable for synthesizing increasingly complex molecular architectures. In this study, we utilized imine DCC chemistry to prepare TPMA-based supramolecular cages for molecular recognition applications. However, the hydrolytic lability of imines limits some applications. We introduced a synthetic strategy that combines the advantages of imine chemistry with the ability to synthesize chiral hydrolytically stable structures through a [3,3]-sigmatropic rearrangement.