Three Switchable Orthogonal Dynamic Covalent Reactions and Complex Networks Based on the Control of Dual Reactivity.

Achieving complexity is central to the creation of chemical systems, inspired by natural systems. Herein we introduce a strategy of switchable orthogonal dynamic covalent chemistry (DCC) toward the regulation of complex dynamic networks. The control of dual reactivity of tautomers and resulting pathways allowed reversible covalent bonding of a large scope of primary amines, secondary amines, alcohols, and thiols with high efficiency. The selection of reaction pathways next enabled the realization of orthogonal but switchable dynamic covalent reactions (DCRs) with nucleophile pairs of amine/alcohol, alcohol/thiol, and amine/thiol by varying protonation and oxidation states. Control experiments confirmed the crucial role of dual reactivity on the stability and switchability of DCRs. The specificity toward amines, alcohols, and thiols, as well as interconversion between their corresponding assemblies, was further accomplished in one vessel, thus creating tunable communicating networks with three types of DCRs. Moreover, the switchable orthogonality combined with differential reactivity of multiple sulfonamides and nucleophiles enhanced the complexity within dynamic libraries. The generality and versatility of our approaches should facilitate their incorporation into many aspects of chemistry endeavors.