Effects of additional ring-fusion site on dual reactivity based dynamic covalent chemistry

Abstract

Tautomers are widespread in organic chemistry, and their unique reactivity allows diverse transformations. In this work, the incorporation of nearby amide ring-fusion site offered a versatile platform for controlling dual reactivity based dynamic covalent chemistry (DCC) of aldehyde ring-chain tautomers. A suite of 2-formylbenzosulfonamide derived tautomers were prepared, and the intramolecular ring-chain equilibrium and intermolecular dynamic covalent reactions along the underlying mechanistic foundation were investigated. By regulating the substituent electronic effect and solvent effect, ring-chain tautomerization equilibrium was readily regulated in solution. The adjacent amide NH participates in intramolecular hydrogen bonding, as revealed by crystal analysis. Furthermore, the addition of acid and the change of solvent allowed turning on/off the intramolecular cyclization from the amide group to create fused ring scaffolds. Finally, the reversible covalent reactions with amine nucleophile reagents maintained the intermolecular reactivity successfully. The molecular and pathway diversity reported herein sets the scene for future design and applications.